Adenosine Receptors and the Kidney (2024)

The publisher's final edited version of this article is available at Handb Exp Pharmacol

2.1 Activation of A₁AR Lowers Glomerular Filtration Rate

Healthy volunteers responded to an intravenous infusion or direct application of adenosine into the renal artery with a reduction in GFR of 15–25% while blood pressure and renal blood flow were unchanged (Edlund and Sollevi 1993; Edlund et al. 1994; Balakrishnan et al. 1996). Adenosine infusion into the renal artery of rats or dogs reduced single-nephron GFR (SNGFR) in superficial nephrons to a larger extent than whole-kidney GFR, indicating that deep-cortical vasodilation (see below) counteracts superficial vasoconstriction (Osswald et al. 1978a, b; Haas and Osswald 1981). Adenosine lowers SNGFR in superficial nephrons due to afferent arteriolar vasoconstriction (Osswald et al. 1978b; Haas and Osswald 1981) (Fig. 1). Direct videometric assessment of pre- and postglomerular arteries using the “split-hydronephrotic” rat kidney technique revealed adenosine-induced constriction of afferent arterioles via high-affinity A₁AR and dilation via activation of both high-affinity A_2AAR and low-affinity A_2BAR (Tang et al. 1999). Whereas activation of A₁AR led to the constriction of mainly afferent arterioles near the glomerulus, A₂AR activation lead to the dilation of mainly postglomerular arteries (Holz and Steinhausen 1987; Dietrich and Steinhausen 1993; Gabriels et al. 2000). A₁AR-mediated afferent arteriolar constriction involves a pertussis toxin-sensitive Gi protein and subsequent activation of phospholipase C, presumably through βγ subunits released from Gαi (Hansen et al. 2003b). A_2AAR-mediated renal vasodilation may involve activation of ATP-regulated potassium channels (Tang et al. 1999) and endothelial nitric oxide synthase (Hansen et al. 2005).

Oral application of the A₁AR antagonist (+)-(R)-[(E)-3-(2-phenylpyrazolo [1,5-a]pyridin-3-yl)acryloyl]-2-piperidine ethanol (FK-453) to healthy male subjects increased GFR by ∼20% without significantly altering effective renal plasma flow or mean arterial blood pressure (Balakrishnan et al. 1993), providing evidence that endogenous adenosine elicits a tonic suppression of GFR through the activation of A₁AR. Consistent with a prominent role of adenosine in the regulation of afferent arteriolar tone, autoregulation of renal blood flow and glomerular filtration rate (i.e., their constancy in spite of changes in renal perfusion pressure) is dependent upon the activation of A₁AR (Hashimoto et al. 2006).

2.2 Factors Modulating Adenosine-Induced Cortical Vasoconstriction

Suppression of the renin–angiotensin system by dietary salt or pharmacological means reduces or blocks the renal vasoconstrictive action of adenosine (Osswald et al. 1975, 1982; Spielman and Osswald 1979; Arend et al. 1985; Macias-Nunez et al. 1985; Dietrich et al. 1991; Dietrich and Steinhausen 1993). In contrast, activation of the renin–angiotensin system potentiates adenosine-induced vasoconstriction and lowering of GFR (Osswald et al. 1975, 1978a, 1982). Further studies identified a mutual dependency and cooperation of adenosine and angiotensin II in producing afferent arteriolar constriction (Weihprecht et al. 1994; Traynor et al. 1998; Hansen et al. 2003a). Adenosine enhances angiotensin II-induced constriction of afferent arterioles by receptor-dependent and -independent pathways. The latter involves adenosine uptake and intracellular effects that increase the calcium sensitivity by phosphorylating the myosin light chain (Lai et al. 2006; Patzak et al. 2007). Moreover, inhibiting the synthesis of vasodilators like nitric oxide (NO) (Barrett and Droppleman 1993; Pflueger et al. 1999b) or prostaglandins (Spielman and Osswald 1978; Pflueger et al. 1999a) increases the sensitivity of the kidney to adenosine-induced vasoconstriction. The outlined interactions can be of clinical relevance.

2.3 Activation of A₂AR Induces Medullary Vasodilation

Intrarenal adenosine infusion in rats initially induces vasoconstriction in all cortical zones; this is followed by persistent superficial cortical vasoconstriction but deep cortical vasodilation (Macias-Nunez et al. 1983; Miyamoto et al. 1988). While A₁AR-mediated afferent arteriolar constriction dominates in superficial nephrons, deep cortical glomeruli, which supply the blood flow to the renal medulla, can respond to adenosine with A₂AR-mediated vasodilation (Inscho et al. 1991; Weihprecht et al. 1992; Inscho 1996; Yaoita et al. 1999; Nishiyama et al. 2001). In accordance, renal interstitial infusion in rats of the A₂AR agonist 2-[p-(2-carboxyethyl)phenethylamino]-5′-N-ethylcarboxamido adenosine (CGS-21680) increased medullary blood flow (Agmon et al. 1993), whereas intramedullary infusion of the selective A₂AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) (but not the A₁AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX)) decreased medullary blood flow (Zou et al. 1999). This indicates that endogenous adenosine dilates medullary vessels and sustains medullary blood flow via activation of A₂AR (Fig. 1).

2.4 Adenosine is a Mediator of Tubuloglomerular Feedback via Activation of A₁AR

The mammalian kidney has a rather high GFR (∼180 l per day in humans). About 99% of the filtered fluid and NaCl are subsequently reabsorbed along the tubular and collecting duct system, such that urinary excretion closely matches intake. As a result, GFR is a significant determinant of renal transport work, and GFR and re-absorption have to be closely coordinated to avoid renal loss or retention of fluid and NaCl. The tubuloglomerular feedback (TGF) is a mechanism that helps to coordinate GFR with the tubular transport activity or capacity. In this mechanism, specialized tubular cells, the macula densa, sense the tubular NaCl load at the end of the thick ascending limb (TAL; where about 85% of the filtered NaCl has been reabsorbed), and induce a change in afferent arteriolar tone such that an inverse relationship is established between the tubular NaCl load and SNGFR of the same nephron. This way, the TGF stabilizes the NaCl load to further distal segments, where the fine regulation of NaCl and fluid balance takes place under systemic neurohumoral control.

The TGF response, in other words an inverse change in SNGFR or glomerular capillary pressure in response to changes in the NaCl concentration at the macula densa, is inhibited by unselective adenosine receptor blockers like theophylline or 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) (Schnermann et al. 1977; Osswald et al. 1980; Franco et al. 1989), as well as by selective A₁AR antagonists like DPCPX, 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902, rolofylline), CVT-124 (the S-enantiomer of the highly selective racemic A₁AR antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)] xanthine), or 6-oxo-3-(2-phenylpyrazolo [1,5-a]pyridin-3-yl)-1(6H)-pyridazinebutanoic acid (FK838) (Franco et al. 1989; Schnermann et al. 1990; Kawabata et al. 1998; Wilcox et al. 1999; Thomson et al. 2000; Ren et al. 2002a). Mice with gene knockout for A₁AR lack the TGF response (Brown et al. 2001; Sun et al. 2001; Vallon et al. 2004), and have an impaired ability to stabilize the Na⁺ delivery to the distal tubule (Vallon et al. 2004). Most importantly, an intact TGF response requires local concentrations of adenosine to fluctuate depending on the NaCl concentration in the tubular fluid at the macula densa, indicating that adenosine serves as a mediator of TGF (Thomson et al. 2000).

In 1980, Osswald and colleagues proposed that adenosine may be a mediator of TGF. Figure 2 illustrates a current model. Changes in luminal concentrations of Na⁺, K⁺, and Cl⁻ alter NaCl uptake by macula densa cells via the furosemide-sensitive Na–K–2Cl cotransporter in the luminal membrane. This triggers basolateral ATP release (Bell et al. 2003; Komlosi et al. 2004) as well as transport-dependent hydrolysis by basolateral Na⁺–K⁺-ATPase (Lorenz et al. 2006) of ATP to AMP. Plasma membrane-bound ectonucleoside triphosphate diphosphohydrolase 1 (CD39) converts ATP and ADP to AMP (Oppermann et al. 2008) and ecto-5′-nucleotidase (CD73) converts extracellular AMP to adenosine (Thomson et al. 2000; Castrop et al. 2004; Ren et al. 2004; Huang et al. 2006). Part of the extracellular adenosine involved in the TGF response is generated independent of ecto-5′-nucleotidase and may reflect direct adenosine release from macula densa cells (Huang et al. 2006). Extracellular adenosine binds to A₁AR at the surface of extraglomerular mesangial cells (Olivera et al. 1989; Weaver and Reppert 1992; Toya et al. 1993; Smith et al. 2001) and increases cytosolic Ca²⁺ concentrations (Olivera et al. 1989). Gap junctions between extraglomerular mesangial cells and smooth muscle cells of glomerular arterioles can transmit intracellular Ca²⁺ transients to these target structures, inducing afferent arteriolar constriction (Iijima et al. 1991; Ren et al. 2002b). Potential candidates for the formation of gap junctions in the juxtaglomerular apparatus include connexins 37, 40, and 43 (Wagner et al. 2007; Takenaka et al. 2008a, b).

4.1 Activation of A₁AR Increases Reabsorption in the Proximal Tubule

Endogenously formed adenosine can stimulate proximal tubular reabsorption of fluid, Na⁺, HCO₃⁻, and phosphate by activation of A₁AR (Takeda et al. 1993; Cai et al. 1994, 1995; Tang and Zhou 2003). Importantly, systemic application of selective A₁AR antagonists (such as CVT-124, DPCPX, KW-3902, or FK-453) elicits diuresis and natriuresis predominantly by inhibiting reabsorption in the proximal tubule in rats and humans (Mizumoto and Karasawa 1993; Balakrishnan et al. 1993; van-Buren et al. 1993; Knight et al. 1993b; Wilcox et al. 1999; Miracle et al. 2007), indicating a tonic stimulation of proximal tubular reabsorption via A₁AR activation (Fig. 1). As a consequence, selective A₁AR antagonists are being developed as eukaliuretic natriuretics in Na⁺-retaining states such as heart failure (see below). A₁AR-mediated increases in proximal tubular reabsorption may involve increases of intracellular Ca²⁺ (Di Sole et al. 2003), reductions of intracellular cAMP levels (Kost Jr et al. 2000), and activation of the Na⁺–H⁺ exchanger (NHE3) (Di Sole et al. 2003).

Similar to selective A₁AR blockade, systemic application or consumption of the unselective adenosine receptor antagonist theophylline or caffeine induces natriuretic and diuretic responses. These responses to theophylline and caffeine are absent in mice lacking A₁AR, strongly suggesting that A₁AR blockade mediates the natriuresis and diuresis in response to these compounds (Rieg et al. 2005).

4.2 Activation of A₁AR Inhibits Reabsorption in Medullary Thick Ascending Limb

In contrast to the proximal tubule, adenosine via activation of A₁AR inhibits NaCl reabsorption in medullary TAL (Torikai 1987; Burnatowska-Hledin and Spielman 1991; Beach and Good 1992). Medullary TAL is a site of adenosine release, and adenosine release in this segment is transport dependent (Beach et al. 1991; Baudouin-Legros et al. 1995) and enhances significantly during hypoxic conditions (Beach et al. 1991). Studies using pharmacological inhibition (Zou et al. 1999) or gene knockout (Vallon et al. 2004) are consistent with a tonic inhibition of Na⁺ re-absorption in medullary TAL by A₁AR activation (Fig. 1). This is relevant since the renal medulla has a low partial oxygen pressure (Brezis and Rosen 1995), and the described inhibitory effects of adenosine on transport work together with its A₂AR-mediated renal medullary vasodilation (see above) to maintain metabolic balance in the renal medulla.

4.3 Effects of Adenosine on Transport in Distal Convolution and Cortical Collecting Duct

In general, natriuretics that act proximal to the aldosterone-sensitive distal nephron stimulate K⁺ secretion in the latter segment and thus increase renal K⁺ excretion. The natriuretic but eukaliuretic effect of A₁AR inhibitors suggests an additional site of action in the aldosterone-sensitive distal nephron, but the exact site of action and the involved mechanisms are unclear.

A₁AR activation can stimulate Mg²⁺ and Ca²⁺ uptake in the cortical collecting duct in vitro (Hoenderop et al. 1998, 1999; Kang et al. 2001), but the clinical relevance (e.g., during pharmacological inhibition of A₁AR) is not known.

4.4 Activation of A₁AR Counteracts Vasopressin Effects in Inner Medullary Collecting Duct

Extracellular adenosine feedback can inhibit vasopressin-induced cAMP-mediated stimulation of Na⁺ and fluid reabsorption in the inner medullary collecting duct (IMCD) (Yagil 1990; Yagil et al. 1994; Rieg et al. 2008) and decrease vasopressin-stimulated electrogenic Cl⁻ secretion through the activation of A₁AR (Moyer et al. 1995). Vasopressin-induced adenosine may derive from the extracellular cAMP–adenosine pathway (Jackson et al. 2003) or follow the cellular release and breakdown of ATP (Vallon 2008). Studies on water transport in knockout mice indicate efficient compensation by other pathways in the absence of A₁AR, including upregulation of ATP-sensitive P2Y₂ receptors (Rieg et al. 2008).

6.1 Radiocontrast Media-Induced Acute Renal Failure: Theophylline and A₁AR Antagonists Induce Protective Effects

Application of radiocontrast media to humans can lead to an impairment of renal function, including a fall in GFR. Concomitant volume and NaCl depletion increases the severity and can result in ARF. Unselective or A₁AR-selective antagonists can prevent renal impairment induced by radiocontrast media, as shown in dogs (Arend et al. 1987), rats (Erley et al. 1997), mice (Lee et al. 2006), and, most importantly, in humans (Erley et al. 1994; Katholi et al. 1995; Kolonko et al. 1998; Kapoor et al. 2002; Huber et al. 2002, 2003). In accordance, mice lacking A₁AR preserved kidney function better, and had lesser renal cortical vacuolization and enhanced survival 24 h after radiocontrast media treatment compared with wild-type mice (Lee et al. 2006). In comparison, dipyridamole, which increases extracellular adenosine concentrations, augmented the severity of renal impairment in response to radio-contrast media in dogs (Arend et al. 1987) and humans (Katholi et al. 1995). Two studies indicated that the unselective adenosine receptor antagonist theophylline is as effective as saline hydration at preventing ARF in response to contrast media, but the benefits of the two maneuvers are not additive (Abizaid et al. 1999; Erley et al. 1999). Thus, use of theophylline can be beneficial in patients where sufficient hydration may be impossible or in patients with a concomitant decrease in renal blood flow (e.g., congestive heart failure or chronic renal insufficiency (Erley et al. 1999; Huber et al. 2002)). A recent meta-analysis of clinical trials concluded that theophylline may reduce the incidence of radiocontrast media-induced nephropathy, and recommended a large, well-designed trial to more adequately assess the role of theophylline in this condition (Bagshaw and Ghali 2005). Notably, unselective or A₁AR-selective antagonists can also prevent renal impairment in response to other nephrotoxic substances (Table 1).

6.2 Ischemia-Reperfusion Injury

Ischemia-reperfusion injury plays a major role in delayed graft function and long-term changes after kidney transplantation. It has become evident that the cellular and molecular mechanisms that operate during ischemia and reperfusion resemble an acute inflammatory response (Gueler et al. 2004). To what extent the acute cellular alterations persist and affect organ function later on remains unclear.

In the kidney, extracellular adenosine derives to a large extent from the extracellular breakdown of ATP and ADP to AMP and adenosine via ectonucleoside triphosphate diphosphohydrolases (ENTPDases) and CD73 (Grenz et al. 2007a, b). Using knockout mouse models for these ectoenzymes, Grenz et al. showed that CD39-dependent nucleotide phosphohydrolysis as well as CD73-dependent adenosine formation serve to protect against renal ischemia-reperfusion injury and to increase the ischemia tolerance of the kidney. In addition, the authors presented evidence that treatment with apyrase or soluble 5′-nucleotidase to increase extracellular adenosine concentrations could serve as potential novel pharmacological approaches to renal diseases precipitated by limited oxygen availability (Grenz et al. 2007a, b).

7.1 Animal Studies

Lucas et al. used a pig model of systolic dysfunction and induction of chronic heart failure by pacer-induced tachycardia. They observed that acute application of the selective A₁AR antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)xanthine (BG9719) (CVT-124) increased creatinine clearance and urinary flow rate and sodium excretion. This was associated with lower pulmonary capillary wedge pressure and pulmonary vascular resistance in the absence of significant changes in mean arterial blood pressure, heart rate or cardiac output compared with vehicle control (Lucas Jr et al. 2002). Similar effects were described by Jackson et al. in aged, lean SHHF/Mcc-fa(cp) rats, a rodent model of hypertensive dilated cardiomyopathy in response to the same compound (Jackson et al. 2001). The rats were pretreated for 72 h before experiments with the loop diuretic furosemide to mimic the clinical setting of chronic diuretic therapy, and were given 1% NaCl as drinking water to reduce dehydration/sodium depletion. Acute application of BG9719 increased GFR and urinary fluid and sodium excretion. In comparison, acute application of furosemide decreased renal blood flow and GFR and increased fractional potassium excretion. Neither drug altered afterload or left ventricular systolic function (+dP/dt (max)); however, furosemide, but not BG9719, decreased preload and attenuated diastolic function (decreased −dP/dt (max), increased tau). Thus, in the setting of left ventricular dysfunction, chronic salt loading and prior loop diuretic treatment, selective A₁AR antagonists are effective diuretic/natriuretic agents that do not induce potassium loss and have a favorable renal hemodynamic/cardiac performance profile (Jackson et al. 2001).

7.2 Human Studies

Gottlieb et al. compared the acute effects of furosemide and BG9719 on renal function in 12 patients categorized as New York Heart Association (NYHA) functional classes II, III or IV (Gottlieb et al. 2000). Both BG9719 and furosemide increased sodium excretion compared with placebo. However, only furosemide lowered GFR. Subsequently, Gottlieb et al. compared BG9719 and furosemide in 63 patients categorized as NYHA functional classes II, III or IV, which despite receiving standard therapy, including furosemide (at least 80 mg daily) and angiotensin-converting enzyme inhibitors, remained edematous (Gottlieb et al. 2002). Patients received 7 h infusions of placebo or BG9719 to yield serum concentrations of 0.1, 0.75, or 2.5 μg ml⁻¹. BG9719 tripled urine output without lowering GFR or inducing kaliuresis. In comparison, furosemide increased urine output eightfold and increased potassium excretion while reducing GFR. Notably, when BG9719 was given with furosemide, GFR remained unaltered compared with placebo and sodium excretion increased further. These results indicate that A₁AR antagonism can preserve renal function while simultaneously promoting natriuresis during acute treatment of heart failure (Gottlieb et al. 2002).

Similar results were more recently reported in studies using the A₁AR antagonist KW-3902 in patients with congestive heart failure and impaired renal function (Dittrich et al. 2007; Givertz et al. 2007). Dittrich et al. assessed baseline GFR and renal plasma flow 3 h before and over 8 h following the intravenous administration of furosemide along with KW-3902 (30 mg) or placebo. After a washout period of 3–8 days (median six days), the crossover portion of the study was performed. KW-3902 increased GFR by 32% and renal plasma flow by 48% compared with placebo. Notably, subjects who initially received KW-3902 had a statistically significant 10 ml min⁻¹ increase in GFR when they returned for the crossover phase compared with the previous baseline. Thus, the increase in GFR persisted for several days longer than predicted by pharmaco*kinetics. These findings suggest that KW-3902 reset the complex network that determines kidney function in these patients, and provided first evidence for potential longer-term benefits of using A₁AR antagonists (Dittrich et al. 2007). Greenberg et al. assessed the effects of the selective A₁AR antagonist 1,3-dipropyl-8-[1-(4-propionate)-bicyclo-[2,2,2]octyl)]xanthine (BG9928) given orally for ten days to 50 patients with heart failure and left ventricular systolic dysfunction who were receiving standard therapy (Greenberg et al. 2007). BG9928 (3–225 mg per day) increased sodium excretion without causing kaliuresis or reducing GFR. Notably, these effects were maintained over the ten-day period. BG9928 at doses of 15, 75, or 225 mg also reduced body weight at the end of the study compared with placebo (Greenberg et al. 2007).

In summary, the abovedescribed acute and short-term studies employing A₁AR antagonists in patients with heart failure yielded promising results. Since A₁AR blockade may increase transport in the semihypoxic medullary TAL, combining A₁AR antagonists with furosemide may potentiate natriuresis while helping to prevent transport-induced medullary hypoxia (Fig. 4). Whereas the presented animal and human studies were acute or short-term treatments, it remains to be determined whether longer-term application of A₁AR antagonism has beneficial effects. These studies should also reveal whether a clinically relevant effect of A₁AR blockade on renin release occurs. Consideration should also be given to the evidence that A₁AR activation is potentially important for protection in response to ischemia of the kidney (see above) and the heart (Cohen and Downey 2008). Apart from these issues, A₁AR blockade is unique in inducing natriuresis without potassium loss and lowering renal vascular resistance independent of all other organs. With regard to preserving renal function, this is an advantage over all vasodilator heart failure therapies that have been tried so far.

• Abizaid AS, Clark CE, Mintz GS, Dosa S, Popma JJ, Pichard AD, Satler LF, Harvey M, Kent KM, Leon MB. Effects of dopamine and aminophylline on contrast-induced acute renal failure after coronary angioplasty in patients with preexisting renal insufficiency. Am J Cardiol. 1999;83:260–263. A5. [PubMed] [Google Scholar]
• Agmon Y, Dinour D, Brezis M. Disparate effects of adenosine A₁- and A₂-receptor agonists on intrarenal blood flow. Am J Physiol. 1993;265:F802–F806. [PubMed] [Google Scholar]
• Arend LJ, Thompson CI, Spielman WS. Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine. Circ Res. 1985;56:242–251. [PubMed] [Google Scholar]
• Arend LJ, Bakris GL, Burnett JC, Jr, Megerian C, Spielman WS. Role for intrarenal adenosine in the renal hemodynamic response to contrast media. J Lab Clin Med. 1987;110:406–411. [PubMed] [Google Scholar]
• Bagshaw SM, Ghali WA. Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Arch Intern Med. 2005;165:1087–1093. [PubMed] [Google Scholar]
• Bakr AF. Prophylactic theophylline to prevent renal dysfunction in newborns exposed to perinatal asphyxia: a study in a developing country. Pediatr Nephrol. 2005;20:1249–1252. [PubMed] [Google Scholar]
• Balakrishnan VS, Coles GA, Williams JD. A potential role for endogenous adenosine in control of human glomerular and tubular function. Am J Physiol. 1993;265:F504–F510. [PubMed] [Google Scholar]
• Balakrishnan VS, Coles GA, Williams JD. Effects of intravenous adenosine on renal function in healthy human subjects. Am J Physiol. 1996;271:F374–F381. [PubMed] [Google Scholar]
• Barrett RJ, Droppleman DA. Interactions of adenosine A₁ receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II. Am J Physiol. 1993;265:F651–F659. [PubMed] [Google Scholar]
• Baudouin-Legros M, Badou A, Paulais M, Hammet M, Teulon J. Hypertonic NaCl enhances adenosine release and hormonal cAMP production in mouse thick ascending limb. Am J Physiol. 1995;269:F103–F109. [PubMed] [Google Scholar]
• Beach RE, Good DW. Effects of adenosine on ion transport in rat medullary thick ascending limb. Am J Physiol. 1992;263:F482–F487. [PubMed] [Google Scholar]
• Beach RE, Watts BA, Good DW, Benedict CR, DuBose TD., Jr Effects of graded oxygen tension on adenosine release by renal medullary and thick ascending limb suspensions. Kidney Int. 1991;39:836–842. [PubMed] [Google Scholar]
• Bell PD, Lapointe JY, Sabirov R, Hayashi S, Peti-Peterdi J, Manabe K, Kovacs G, Okada Y. Macula densa cell signaling involves ATP release through a maxi anion channel. Proc Natl Acad Sci USA. 2003;100:4322–4327. [PMC free article] [PubMed] [Google Scholar]
• Benoehr P, Krueth P, Bokemeyer C, Grenz A, Osswald H, Hartmann JT. Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial. J Am Soc Nephrol. 2005;16:452–458. [PubMed] [Google Scholar]
• Bidani AK, Churchill PC. Aminophylline ameliorates glycerol-induced acute renal failure in rats. Can J Physiol Pharmacol. 1983;61:567–571. [PubMed] [Google Scholar]
• Bidani AK, Churchill PC, Packer W. Theophylline-induced protection in myoglobinuric acute renal failure: further characterization. Can J Physiol Pharmacol. 1987;65:42–45. [PubMed] [Google Scholar]
• Bowmer CJ, Collis MG, Yates MS. Effect of the adenosine antagonist 8-phenyltheophylline on glycerol-induced acute renal failure in the rat. Br J Pharmacol. 1986;88:205–212. [PMC free article] [PubMed] [Google Scholar]
• Brezis M, Rosen S. Hypoxia of the renal medulla: its implications for disease. N Engl J Med. 1995;332:647–655. [PubMed] [Google Scholar]
• Brown R, Ollerstam A, Johansson B, Skott O, Gebre-Medhin S, Fredholm B, Persson AE. Abolished tubuloglomerular feedback and increased plasma renin in adenosine A₁ receptor-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2001;281:R1362–R1367. [PubMed] [Google Scholar]
• Burnatowska-Hledin MA, Spielman WS. Effects of adenosine on cAMP production and cytosolic Ca²⁺ in cultured rabbit medullary thick limb cells. Am J Physiol. 1991;260:C143–C150. [PubMed] [Google Scholar]
• Cai H, Batuman V, Puschett DB, Puschett JB. Effect of KW-3902, a novel adenosine A₁ receptor antagonist, on sodium-dependent phosphate and glucose transport by the rat renal proximal tubular cell. Life Sci. 1994;55:839–845. [PubMed] [Google Scholar]
• Cai H, Puschett DB, Guan S, Batuman V, Puschett JB. Phosphate transport inhibition by KW-3902, an adenosine A₁ receptor antagonist, is mediated by cyclic adenosine monophosphate. Am J Kidney Dis. 1995;26:825–830. [PubMed] [Google Scholar]
• Castrop H, Huang Y, Hashimoto S, Mizel D, Hansen P, Theilig F, Bachmann S, Deng C, Briggs J, Schnermann J. Impairment of tubuloglomerular feedback regulation of GFR in ecto-5′-nucleotidase/CD73-deficient mice. J Clin Invest. 2004;114:634–642. [PMC free article] [PubMed] [Google Scholar]
• Churchill PC, Bidani A. Renal effects of selective adenosine receptor agonists in anesthetized rats. Am J Physiol. 1987;252:F299–F303. [PubMed] [Google Scholar]
• Churchill PC, Churchill MC. A₁ and A₂ adenosine receptor activation inhibits and stimulates renin secretion of rat renal cortical slices. J Pharmacol Exp Ther. 1985;232:589–594. [PubMed] [Google Scholar]
• Cohen MV, Downey JM. Adenosine: trigger and mediator of cardioprotection. Basic Res Cardiol. 2008;103:203–215. [PubMed] [Google Scholar]
• Day YJ, Huang L, McDuffie MJ, Rosin DL, Ye H, Chen JF, Schwarzschild MA, Fink JS, Linden J, Okusa MD. Renal protection from ischemia mediated by A_2A adenosine receptors on bone marrow-derived cells. J Clin Invest. 2003;112:883–891. [PMC free article] [PubMed] [Google Scholar]
• Dietrich MS, Steinhausen M. Differential reactivity of cortical and juxtaglomerullary glomeruli to adenosine-1 and adenosine-2 receptor stimulation and angiotensin converting-enzyme inhibition. Microvasc Res. 1993;45:122–133. [PubMed] [Google Scholar]
• Dietrich MS, Endlich K, Parekh N, Steinhausen M. Interaction between adenosine and angiotensin II in renal microcirculation. Microvasc Res. 1991;41:275–288. [PubMed] [Google Scholar]
• Dinour D, Brezis M. Effects of adenosine on intrarenal oxygenation. Am J Physiol. 1991;261:F787–F791. [PubMed] [Google Scholar]
• Di Sole F, Cerull R, Petzke S, Casavola V, Burckhardt G, Helmle-Kolb C. Bimodal acute effects of A₁ adenosine receptor activation on Na⁺/H⁺ exchanger 3 in opossum kidney cells. J Am Soc Nephrol. 2003;14:1720–1730. [PubMed] [Google Scholar]
• Dittrich HC, Gupta DK, Hack TC, Dowling T, Callahan J, Thomson S. The effect of KW-3902, an adenosine A₁ receptor antagonist, on renal function and renal plasma flow in ambulatory patients with heart failure and renal impairment. J Card Fail. 2007;13:609–617. [PubMed] [Google Scholar]
• Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol. 2000;35:681–689. [PubMed] [Google Scholar]
• Edlund A, Sollevi A. Renal effects of i.v. adenosine infusion in humans. Clin Physiol. 1993;13:361–371. [PubMed] [Google Scholar]
• Edlund A, Ohlsen H, Sollevi A. Renal effects of local infusion of adenosine in man. Clin Sci Colch. 1994;87:143–149. [PubMed] [Google Scholar]
• Erley CM, Duda SH, Schlepckow S, Koehler J, Huppert PE, Strohmaier WL, Bohle A, Risler T, Osswald H. Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application. Kidney Int. 1994;45:1425–1431. [PubMed] [Google Scholar]
• Erley CM, Heyne N, Burgert K, Langanke J, Risler T, Osswald H. Prevention of radiocontrast-induced nephropathy by adenosine antagonists in rats with chronic nitric oxide deficiency. J Am Soc Nephrol. 1997;8:1125–1132. [PubMed] [Google Scholar]
• Erley CM, Duda SH, Rehfuss D, Scholtes B, Bock J, Muller C, Osswald H, Risler T. Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline. Nephrol Dial Transplant. 1999;14:1146–1149. [PubMed] [Google Scholar]
• Ezeamuzie CI. Involvement of A(3) receptors in the potentiation by adenosine of the inhibitory effect of theophylline on human eosinophil degranulation: possible novel mechanism of the antiinflammatory action of theophylline. Biochem Pharmacol. 2001;61:1551–1559. [PubMed] [Google Scholar]
• Forman DE, Butler J, Wang Y, Abraham WT, O’Connor CM, Gottlieb SS, Loh E, Massie BM, Rich MW, Stevenson LW, Young JB, Krumholz HM. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol. 2004;43:61–67. [PubMed] [Google Scholar]
• Franco M, Bell PD, Navar LG. Effect of adenosine A₁ analogue on tubuloglomerular feedback mechanism. Am J Physiol. 1989;257:F231–F236. [PubMed] [Google Scholar]
• Funaya H, Kitakaze M, Node K, Minamino T, Komamura K, Hori M. Plasma adenosine levels increase in patients with chronic heart failure. Circulation. 1997;95:1363–1365. [PubMed] [Google Scholar]
• Gabriels G, Endlich K, Rahn KH, Schlatter E, Steinhausen M. In vivo effects of diadenosine polyphosphates on rat renal microcirculation. Kidney Int. 2000;57:2476–2484. [PubMed] [Google Scholar]
• Garcia GE, Truong LD, Li P, Zhang P, Du J, Chen JF, Feng L. Adenosine A_2A receptor activation and macrophage-mediated experimental glomerulonephritis. FASEB J. 2008;22:445–454. [PMC free article] [PubMed] [Google Scholar]
• Gerkens JF, Heidemann HT, Jackson EK, Branch RA. Effect of aminophylline on amphotericin B nephrotoxicity in the dog. J Pharmacol Exp Ther. 1983;224:609–613. [PubMed] [Google Scholar]
• Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC. The effects of KW-3902, an adenosine A₁-receptor antagonist on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol. 2007;50:1551–1560. [PubMed] [Google Scholar]
• Gottlieb SS, Skettino SL, Wolff A, Beckman E, Fisher ML, Freudenberger R, Gladwell T, Marshall J, Cines M, Bennett D, Liittschwager EB. Effects of BG9719 (CVT-124), an A₁-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure. J Am Coll Cardiol. 2000;35:56–59. [PubMed] [Google Scholar]
• Gottlieb SS, Brater DC, Thomas I, Havranek E, Bourge R, Goldman S, Dyer F, Gomez M, Bennett D, Ticho B, Beckman E, Abraham WT. BG9719 (CVT-124), an A₁ adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation. 2002;105:1348–1353. [PubMed] [Google Scholar]
• Gouyon JB, Guignard JP. Theophylline prevents the hypoxemia-induced renal hemodynamic changes in rabbits. Kidney Int. 1988;33:1078–1083. [PubMed] [Google Scholar]
• Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT. Effects of multiple oral doses of an A₁ adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study. J Am Coll Cardiol. 2007;50:600–606. [PubMed] [Google Scholar]
• Grenz A, Zhang H, Eckle T, Mittelbronn M, Wehrmann M, Kohle C, Kloor D, Thompson LF, Osswald H, Eltzschig HK. Protective role of ecto-5′-nucleotidase (CD73) in renal ischemia. J Am Soc Nephrol. 2007a;18:833–845. [PubMed] [Google Scholar]
• Grenz A, Zhang H, Hermes M, Eckle T, Klingel K, Huang DY, Muller CE, Robson SC, Osswald H, Eltzschig HK. Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury. FASEB J. 2007b;21:2863–2873. [PubMed] [Google Scholar]
• Grenz A, Osswald H, Eckle T, Yang D, Zhang H, Tran ZV, Klingel K, Ravid K, Eltzschig HK. The reno-vascular A_2B adenosine receptor protects the kidney from ischemia. PLoS Med. 2008;5:e137. [PMC free article] [PubMed] [Google Scholar]
• Gueler F, Gwinner W, Schwarz A, Haller H. Long-term effects of acute ischemia and reperfusion injury. Kidney Int. 2004;66:523–527. [PubMed] [Google Scholar]
• Haas JA, Osswald H. Adenosine induced fall in glomerular capillary pressure. Effect of ureteral obstruction and aortic constriction in the Munich–Wistar rat kidney. Naunyn–Schmiedeberg’s Arch Pharmacol. 1981;317:86–89. [PubMed] [Google Scholar]
• Hansen PB, Hashimoto S, Briggs J, Schnermann J. Attenuated renovascular constrictor responses to angiotensin II in adenosine 1 receptor knockout mice. Am J Physiol Regul Integr Comp Physiol. 2003a;285:R44–R49. [PubMed] [Google Scholar]
• Hansen PB, Castrop H, Briggs J, Schnermann J. Adenosine induces vasoconstriction through Gi-dependent activation of phospholipase C in isolated perfused afferent arterioles of mice. J Am Soc Nephrol. 2003b;14:2457–2465. [PubMed] [Google Scholar]
• Hansen PB, Hashimoto S, Oppermann M, Huang Y, Briggs JP, Schnermann J. Vasoconstrictor and vasodilator effects of adenosine in the mouse kidney due to preferential activation of A₁ or A₂ adenosine receptors. J Pharmacol Exp Ther. 2005;315:1150–1157. [PubMed] [Google Scholar]
• Hashimoto S, Huang Y, Briggs J, Schnermann J. Reduced autoregulatory effectiveness in adenosine 1 receptor-deficient mice. Am J Physiol Renal Physiol. 2006;290:F888–F891. [PubMed] [Google Scholar]
• Heidemann HT, Gerkens JF, Jackson EK, Branch RA. Effect of aminophylline on renal vaso-constriction produced by amphotericin B in the rat. Naunyn–Schmiedeberg’s Arch Pharmacol. 1983;324:148–152. [PubMed] [Google Scholar]
• Heidemann HT, Muller S, Mertins L, Stepan G, Hoffmann K, Ohnhaus EE. Effect of aminophylline on cisplatin nephrotoxicity in the rat. Br J Pharmacol. 1989;97:313–318. [PMC free article] [PubMed] [Google Scholar]
• Helmlinger J. Das experimentell erzeugte akute ischämische Nierenversagen bei der Ratte. University of Aachen; Germany: 1979. Dissertation. [Google Scholar]
• Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, Hampton JR, van Veldhuisen DJ. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000;102:203–210. [PubMed] [Google Scholar]
• Hoenderop JG, Hartog A, Willems PH, Bindels RJ. Adenosine-stimulated Ca²⁺ reabsorption is mediated by apical A₁ receptors in rabbit cortical collecting system. Am J Physiol. 1998;274:F736–F743. [PubMed] [Google Scholar]
• Hoenderop JGJ, De Pont JJHH, Bindels RJM, Willems PHGM. Hormone-stimulated Ca²⁺ reabsorption in rabbit kidney cortical collecting system is cAMP-independent and involves a phorbol ester-insensitive PKC isotype. Kidney Int. 1999;55:225–233. [PubMed] [Google Scholar]
• Holz FG, Steinhausen M. Renovascular effects of adenosine receptor agonists. Renal Physiol. 1987;10:272–282. [PubMed] [Google Scholar]
• Huang DY, Vallon V, Zimmermann H, Koszalka P, Schrader J, Osswald H. Ecto-5′-nucleotidase (cd73)-dependent and -independent generation of adenosine participates in the mediation of tubuloglomerular feedback in vivo. Am J Physiol Renal Physiol. 2006;291:F282–F288. [PubMed] [Google Scholar]
• Huber W, Ilgmann K, Page M, Hennig M, Schweigart U, Jeschke B, Lutilsky L, Weiss W, Salmhofer H, Classen M. Effect of theophylline on contrast material-nephropathy in patients with chronic renal insufficiency: controlled, randomized, double-blinded study. Radiology. 2002;223:772–779. [PubMed] [Google Scholar]
• Huber W, Schipek C, Ilgmann K, Page M, Hennig M, Wacker A, Schweigart U, Lutilsky L, Valina C, Seyfarth M, Schomig A, Classen M. Effectiveness of theophylline prophylaxis of renal impairment after coronary angiography in patients with chronic renal insufficiency. Am J Cardiol. 2003;91:1157–1162. [PubMed] [Google Scholar]
• Iijima K, Moore LC, Goligorsky MS. Syncytial organization of cultured rat mesangial cells. Am J Physiol. 1991;260:F848–F855. [PubMed] [Google Scholar]
• Inscho EW. Purinoceptor-mediated regulation of the renal microvasculature. J Auton Pharmacol. 1996;16:385–388. [PubMed] [Google Scholar]
• Inscho EW, Carmines PK, Navar LG. Juxtamedullary afferent arteriolar responses to P1 and P2 purinergic stimulation. Hypertension. 1991;17:1033–1037. [PubMed] [Google Scholar]
• Ishikawa I, Shikura N, Takada K. Amelioration of glycerol-induced acute renal failure in rats by an adenosine A₁ receptor antagonist (FR-113453) Renal Fail. 1993;15:1–5. [PubMed] [Google Scholar]
• Itoh S, Carretero OA, Murray RD. Possible role of adenosine in the macula densa mechanism of renin release in rabbits. J Clin Invest. 1985;76:1412–1417. [PMC free article] [PubMed] [Google Scholar]
• Jackson EK, Raghvendra DK. The extracellular cyclic AMP-adenosine pathway in renal physiology. Annu Rev Physiol. 2004;66:571–599. [PubMed] [Google Scholar]
• Jackson EK, Kost CK, Jr, Herzer WA, Smits GJ, Tofovic SP. A(1) receptor blockade induces natriuresis with a favorable renal hemodynamic profile in SHHF/Mcc-fa(cp) rats chronically treated with salt and furosemide. J Pharmacol Exp Ther. 2001;299:978–987. [PubMed] [Google Scholar]
• Jackson EK, Mi Z, Zhu C, Dubey RK. Adenosine biosynthesis in the collecting duct. J Pharmacol Exp Ther. 2003;307:888–896. [PubMed] [Google Scholar]
• Joo JD, Kim M, Horst P, Kim J, D’Agati VD, Emala CW, Sr, Lee HT. Acute and delayed renal protection against renal ischemia and reperfusion injury with A₁ adenosine receptors. Am J Physiol Renal Physiol. 2007;293:F1847–F1857. [PubMed] [Google Scholar]
• Kang HS, Kerstan D, Dai LJ, Ritchie G, Quamme GA. Adenosine modulates Mg(2+) uptake in distal convoluted tubule cells via A(1) and A(2) purinoceptors. Am J Physiol Renal Physiol. 2001;281:F1141–F1147. [PubMed] [Google Scholar]
• Kapoor A, Kumar S, Gulati S, Gambhir S, Sethi RS, Sinha N. The role of theophylline in contrast-induced nephropathy: a case–control study. Nephrol Dial Transplant. 2002;17:1936–1941. [PubMed] [Google Scholar]
• Katholi RE, Taylor GJ, McCann WP, Woods WT, Jr, Womack KA, McCoy CD, Katholi CR, Moses HW, Mishkel GJ, Lucore CL, et al. Nephrotoxicity from contrast media: attenuation with theophylline. Radiology. 1995;195:17–22. [PubMed] [Google Scholar]
• Kawabata M, Ogawa T, Takabatake T. Control of rat glomerular microcirculation by juxtaglomerular adenosine A₁ receptors. Kidney Int. 1998;67(Suppl):S228–S230. [PubMed] [Google Scholar]
• Kellett R, Bowmer CJ, Collis MG, Yates MS. Amelioration of glycerol-induced acute renal failure in the rat with 8-cyclopentyl-1,3-dipropylxanthine. Br J Pharmacol. 1989;98:1066–1074. [PMC free article] [PubMed] [Google Scholar]
• Kim SM, Mizel D, Huang YG, Briggs JP, Schnermann J. Adenosine as a mediator of macula densa-dependent inhibition of renin secretion. Am J Physiol Renal Physiol. 2006;290:F1016–F1023. [PubMed] [Google Scholar]
• Knight RJ, Collis MG, Yates MS, Bowmer CJ. Amelioration of cisplatin-induced acute renal failure with 8-cyclopentyl-1,3-dipropylxanthine. Br J Pharmacol. 1991;104:1062–1068. [PMC free article] [PubMed] [Google Scholar]
• Knight RJ, Bowmer CJ, Yates MS. Effect of the selective A₁ adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine on acute renal dysfunction induced by Escherichia coli endotoxin in rats. J Pharm Pharmacol. 1993a;45:979–984. [PubMed] [Google Scholar]
• Knight RJ, Bowmer CJ, Yates MS. The diuretic action of 8-cyclopentyl-1,3-dipropylxanthine, a selective A₁ adenosine receptor antagonist. Br J Pharmacol. 1993b;109(1):271–277. [PMC free article] [PubMed] [Google Scholar]
• Kolonko A, Wiecek A, Kokot F. The nonselective adenosine antagonist theophylline does prevent renal dysfunction induced by radiographic contrast agents. J Nephrol. 1998;11:151–156. [PubMed] [Google Scholar]
• Komlosi P, Peti-Peterdi J, Fuson AL, Fintha A, Rosivall L, Bell PD. Macula densa basolateral ATP release is regulated by luminal [NaCl] and dietary salt intake. Am J Physiol Renal Physiol. 2004;286:F1054–F1058. [PubMed] [Google Scholar]
• Kost CK, Jr, Herzer WA, Rominski BR, Mi Z, Jackson EK. Diuretic response to adenosine A(1) receptor blockade in normotensive and spontaneously hypertensive rats: role of pertussis toxin-sensitive G-proteins. J Pharmacol Exp Ther. 2000;292:752–760. [PubMed] [Google Scholar]
• Lai EY, Martinka P, Fahling M, Mrowka R, Steege A, Gericke A, Sendeski M, Persson PB, Persson AE, Patzak A. Adenosine restores angiotensin II-induced contractions by receptor-independent enhancement of calcium sensitivity in renal arterioles. Circ Res. 2006;99:1117–1124. [PubMed] [Google Scholar]
• Lee HT, Emala CW. Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A(1) and A(3) receptors. Am J Physiol. 2000;278:F380–F387. [PubMed] [Google Scholar]
• Lee HT, Emala CW. Protein kinase C and G(i/o) proteins are involved in adenosine- and ischemic preconditioning-mediated renal protection. J Am Soc Nephrol. 2001a;12:233–240. [PubMed] [Google Scholar]
• Lee HT, Emala CW. Systemic adenosine given after ischemia protects renal function via A(2a) adenosine receptor activation. Am J Kidney Dis. 2001b;38:610–618. [PubMed] [Google Scholar]
• Lee HT, Ota-Setlik A, Xu H, D’Agati VD, Jacobson MA, Emala CW. A₃ adenosine receptor knockout mice are protected against ischemia- and myoglobinuria-induced renal failure. Am J Physiol Renal Physiol. 2003;284:F267–F273. [PubMed] [Google Scholar]
• Lee HT, Gallos G, Nasr SH, Emala CW. A₁ adenosine receptor activation inhibits inflammation, necrosis, and apoptosis after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol. 2004a;15:102–111. [PubMed] [Google Scholar]
• Lee HT, Xu H, Nasr SH, Schnermann J, Emala CW. A₁ adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion. Am J Physiol Renal Physiol. 2004b;286:F298–F306. [PubMed] [Google Scholar]
• Lee HT, Jan M, Bae SC, Joo JD, Goubaeva FR, Yang J, Kim M. A₁ adenosine receptor knock-out mice are protected against acute radiocontrast nephropathy in vivo. Am J Physiol Renal Physiol. 2006;290:F1367–F1375. [PubMed] [Google Scholar]
• Lee HT, Kim M, Jan M, Penn RB, Emala CW. Renal tubule necrosis and apoptosis modulation by A₁ adenosine receptor expression. Kidney Int. 2007;71:1249–1261. [PubMed] [Google Scholar]
• Lin JJ, Churchill PC, Bidani AK. Effect of theophylline on the initiation phase of postischemic acute renal failure in rats. J Lab Clin Med. 1986;108:150–154. [PubMed] [Google Scholar]
• Lin JJ, Churchill PC, Bidani AK. The effect of dipyridamole on the initiation phase of postischemic acute renal failure in rats. Can J Physiol Pharmacol. 1987;65:1491–1495. [PubMed] [Google Scholar]
• Lin JJ, Churchill PC, Bidani AK. Theophylline in rats during maintenance phase of postischemic acute renal failure. Kidney Int. 1988;33:24–28. [PubMed] [Google Scholar]
• Lorenz JN, Weihprecht H, He XR, Skott O, Briggs JP, Schnermann J. Effects of adenosine and angiotensin on macula densa-stimulated renin secretion. Am J Physiol. 1993;265:F187–F194. [PubMed] [Google Scholar]
• Lorenz JN, Dostanic-Larson I, Shull GE, Lingrel JB. Ouabain inhibits tubuloglomerular feedback in mutant mice with ouabain-sensitive alpha1 Na, K-ATPase. J Am Soc Nephrol. 2006;17:2457–2463. [PubMed] [Google Scholar]
• Lucas DG, Jr, Hendrick JW, Sample JA, Mukherjee R, Escobar GP, Smits GJ, Crawford FA, Jr, Spinale FG. Cardiorenal effects of adenosine subtype 1 (A1) receptor inhibition in an experimental model of heart failure. J Am Coll Surg. 2002;194:603–609. [PubMed] [Google Scholar]
• Macias-Nunez JF, Fiksen-Olsen MJ, Romero JC, Knox FG. Intrarenal blood flow distribution during adenosine-mediated vasoconstriction. Am J Physiol. 1983;244:H138–H141. [PubMed] [Google Scholar]
• Macias-Nunez JF, Garcia Iglesias C, Santos JC, Sanz E, Lopez-Novoa JM. Influence of plasma renin content, intrarenal angiotensin II, captopril, and calcium channel blockers on the vasoconstriction and renin release promoted by adenosine in the kidney. J Lab Clin Med. 1985;106:562–567. [PubMed] [Google Scholar]
• Mahon NG, Blackstone EH, Francis GS, Starling RC, III, Young JB, Lauer MS. The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure. J Am Coll Cardiol. 2002;40:1106–1113. [PubMed] [Google Scholar]
• Miracle CM, Rieg T, Blantz RC, Vallon V, Thomson SC. Combined effects of carbonic anhydrase inhibitor and adenosine A₁ receptor antagonist on hemodynamic and tubular function in the kidney. Kidney Blood Press Res. 2007;30:388–399. [PMC free article] [PubMed] [Google Scholar]
• Miyamoto M, Yagil Y, Larson T, Robertson C, Jamison RL. Effects of intrarenal adenosine on renal function and medullary blood flow in the rat. Am J Physiol. 1988;255:F1230–F1234. [PubMed] [Google Scholar]
• Mizumoto H, Karasawa A. Renal tubular site of action of KW-3902, a novel adenosine A-1-receptor antagonist, in anesthetized rats. Jpn J Pharmacol. 1993;31(3):251–253. [PubMed] [Google Scholar]
• Modlinger PS, Welch WJ. Adenosine A₁ receptor antagonists and the kidney. Curr Opin Nephrol Hypertens. 2003;12:497–502. [PubMed] [Google Scholar]
• Moyer BD, McCoy DE, Lee B, Kizer N, Stanton BA. Adenosine inhibits arginine vasopressin-stimulated chloride secretion in a mouse IMCD cell line (mIMCD-K2) Am J Physiol. 1995;269:F884–F891. [PubMed] [Google Scholar]
• Nagashima K, Kusaka H, Karasawa A. Protective effects of KW-3902, an adenosine A₁-receptor antagonist, against cisplatin-induced acute renal failure in rats. Jpn J Pharmacol. 1995;67:349–357. [PubMed] [Google Scholar]
• Newman WH, Grossman SJ, Frankis MB, Webb JG. Increased myocardial adenosine release in heart failure. J Mol Cell Cardiol. 1984;16:577–580. [PubMed] [Google Scholar]
• Nishiyama A, Miyatake A, Aki Y, f*ckui T, Rahman M, Kimura S, Abe Y. Adenosine A(1) receptor antagonist KW-3902 prevents hypoxia-induced renal vasoconstriction. J Pharmacol Exp Ther. 1999;291:988–993. [PubMed] [Google Scholar]
• Nishiyama A, Inscho EW, Navar LG. Interactions of adenosine A₁ and A_2a receptors on renal microvascular reactivity. Am J Physiol Renal Physiol. 2001;280:F406–F414. [PubMed] [Google Scholar]
• Okusa MD, Linden J, Macdonald T, Huang L. Selective A_2A adenosine receptor activation reduces ischemia-reperfusion injury in rat kidney. Am J Physiol. 1999;277:F404–F412. [PubMed] [Google Scholar]
• Olivera A, Lamas S, Rodriguez-Puyol D, Lopez-Novoa JM. Adenosine induces mesangial cell contraction by an A₁-type receptor. Kidney Int. 1989;35:1300–1305. [PubMed] [Google Scholar]
• Oppermann M, Friedman DJ, Faulhaber-Walter R, Mizel D, Castrop H, Enjyoji K, Robson SC, Schnermann JB. Tubuloglomerular feedback and renin secretion in NTPDase1/CD39-deficient mice. Am J Physiol Renal Physiol. 2008;294:F965–F970. [PubMed] [Google Scholar]
• Osswald H, Vallon V. Adenosine and tubuloglomerular feedback in the pathophysiology of acute renal failure. In: Ronco C, Bellomo R, Kellum JA, editors. Critical care nephrology. 2nd 2008. [Google Scholar]
• Osswald H, Schmitz HJ, Heidenreich O. Adenosine response of the rat kidney after saline loading, sodium restriction and hemorrhagia. Pflügers Arch. 1975;357:323–333. [PubMed] [Google Scholar]
• Osswald H, Schmitz HJ, Kemper R. Renal action of adenosine: effect on renin secretion in the rat. Naunyn–Schmiedeberg’s Arch Pharmacol. 1978a;303:95–99. [PubMed] [Google Scholar]
• Osswald H, Spielman WS, Knox FG. Mechanism of adenosine-mediated decreases in glomerular filtration rate in dogs. Circ Res. 1978b;43:465–469. [PubMed] [Google Scholar]
• Osswald H, Helmlinger J, Jendralski A, Abrar B. Improvement of renal function by theophylline in acute renal failure of the rat. Naunyn–Schmiedebergs Arch Pharmacol. 1979;307(Suppl):R 47. [Google Scholar]
• Osswald H, Nabakowski G, Hermes H. Adenosine as a possible mediator of metabolic control of glomerular filtration rate. Int J Biochem. 1980;12:263–267. [PubMed] [Google Scholar]
• Osswald H, Hermes H, Nabakowski G. Role of adenosine in signal transmission of tubuloglomerular feedback. Kidney Int. 1982;22(Suppl 12):S136–S142. [PubMed] [Google Scholar]
• Panjehshahin MR, Munsey TS, Collis MG, Bowmer CJ, Yates MS. Further characterization of the protective effect of 8-cyclopentyl-1,3-dipropylxanthine on glycerol-induced acute renal failure in the rat. J Pharm Pharmacol. 1992;44:109–113. [PubMed] [Google Scholar]
• Patzak A, Lai EY, Fahling M, Sendeski M, Martinka P, Persson PB, Persson AE. Adenosine enhances long term the contractile response to angiotensin II in afferent arterioles. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2232–R2242. [PubMed] [Google Scholar]
• Pflueger AC, Gross JM, Knox FG. Adenosine-induced renal vasoconstriction in diabetes mellitus rats: role of prostaglandins. Am J Physiol. 1999a;277:R1410–R1417. [PubMed] [Google Scholar]
• Pflueger AC, Osswald H, Knox FG. Adenosine-induced renal vasoconstriction in diabetes mellitus rats: role of nitric oxide. Am J Physiol. 1999b;276:F340–F346. [PubMed] [Google Scholar]
• Ren Y, Arima S, Carretero OA, Ito S. Possible role of adenosine in macula densa control of glomerular hemodynamics. Kidney Int. 2002a;61:169–176. [PubMed] [Google Scholar]
• Ren Y, Carretero OA, Garvin JL. Role of mesangial cells and gap junctions in tubuloglomerular feedback. Kidney Int. 2002b;62:525–531. [PubMed] [Google Scholar]
• Ren Y, Garvin JL, Liu R, Carretero OA. Role of macula densa adenosine triphosphate (ATP) in tubuloglomerular feedback. Kidney Int. 2004;66:1479–1485. [PubMed] [Google Scholar]
• Rieg T, Steigele H, Schnermann J, Richter K, Osswald H, Vallon V. Requirement of intact adenosine A₁ receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. J Pharmacol Exp Ther. 2005;313:403–409. [PubMed] [Google Scholar]
• Rieg T, Schnermann J, Vallon V. Adenosine A₁ receptors determine effects of caffeine on total fluid intake but not caffeine appetite. Eur J Pharmacol. 2007;555:174–177. [PubMed] [Google Scholar]
• Rieg T, Pothula K, Schroth J, Satriano J, Osswald H, Schnermann J, Insel PA, Bundey RA, Vallon V. Vasopressin regulation of inner medullary collecting ducts and compensatory changes in mice lacking adenosine A₁ receptors. Am J Physiol Renal Physiol. 2008;294:F638–F644. [PubMed] [Google Scholar]
• Schnermann J, Osswald H, Hermle M. Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat kidney. Pflügers Arch. 1977;369:39–48. [PubMed] [Google Scholar]
• Schnermann J, Weihprecht H, Briggs JP. Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade. Am J Physiol. 1990;258:F553–F561. [PubMed] [Google Scholar]
• Schweda F, Wagner C, Kramer BK, Schnermann J, Kurtz A. Preserved macula densa-dependent renin secretion in A₁ adenosine receptor knockout mice. Am J Physiol Renal Physiol. 2003;284:F770–F777. [PubMed] [Google Scholar]
• Smith JA, Whitaker EM, Bowmer CJ, Yates MS. Differential expression of renal adenosine A(1) receptors induced by acute renal failure. Biochem Pharmacol. 2000;59:727–732. [PubMed] [Google Scholar]
• Smith JA, Sivaprasadarao A, Munsey TS, Bowmer CJ, Yates MS. Immunolocalisation of adenosine A(1) receptors in the rat kidney. Biochem Pharmacol. 2001;61:237–244. [PubMed] [Google Scholar]
• Spielman WS, Osswald H. Characterization of the postocclusive response of renal blood flow in the cat. Am J Physiol. 1978;235:F286–F290. [PubMed] [Google Scholar]
• Spielman WS, Osswald H. Blockade of postocclusive renal vasoconstriction by an angiotensin II antagonist: evidence for an angiotensin–adenosine interaction. Am J Physiol. 1979;237:F463–F467. [PubMed] [Google Scholar]
• Sun D, Samuelson LC, Yang T, Huang Y, Paliege A, Saunders T, Briggs J, Schnermann J. Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking adenosine 1 receptors. Proc Natl Acad Sci USA. 2001;98:9983–9988. [PMC free article] [PubMed] [Google Scholar]
• Suzuki F, Shimada J, Mizumoto H, Karasawa A, Kubo K, Nonaka H, Ishii A, Kawakita T. Adenosine A₁ antagonists. 2. Structure–activity relationships on diuretic activities and protective effects against acute renal failure. J Med Chem. 1992;35:3066–3075. [PubMed] [Google Scholar]
• Tagawa H, Vander AJ. Effects of adenosine compounds on renal function and renin secretion in dogs. Circ Res. 1970;26:327–338. [PubMed] [Google Scholar]
• Takeda M, Yosh*tomi K, Imai M. Regulation of Na(+)–3HCO₃–cotransport in rabbit proximal convoluted tubule via adenosine A₁ receptor. Am J Physiol. 1993;265:F511–F519. [PubMed] [Google Scholar]
• Takenaka T, Inoue T, Kanno Y, Okada H, Hill CE, Suzuki H. Connexins 37 and 40 transduce purinergic signals mediating renal autoregulation. Am J Physiol Regul Integr Comp Physiol. 2008a;294:R1–R11. [PubMed] [Google Scholar]
• Takenaka T, Inoue T, Kanno Y, Okada H, Meaney KR, Hill CE, Suzuki H. Expression and role of connexins in the rat renal vasculature. Kidney Int. 2008b;73:415–422. [PubMed] [Google Scholar]
• Tang L, Parker M, Fei Q, Loutzenhiser R. Afferent arteriolar adenosine A_2a receptors are coupled to KATP in in vitro perfused hydronephrotic rat kidney. Am J Physiol. 1999;277:F926–F933. [PubMed] [Google Scholar]
• Tang Y, Zhou L. Characterization of adenosine A₁ receptors in human proximal tubule epithelial (HK-2) cells. Receptor Channel. 2003;9:67–75. [PubMed] [Google Scholar]
• Thomson S, Bao D, Deng A, Vallon V. Adenosine formed by 5′-nucleotidase mediates tubuloglomerular feedback. J Clin Invest. 2000;106:289–298. [PMC free article] [PubMed] [Google Scholar]
• Torikai S. Effect of phenylisopropyladenosine on vasopressin-dependent cyclic AMP generation in defined nephron segments from rat. Renal Physiol. 1987;10:33–39. [PubMed] [Google Scholar]
• Toya Y, Umemura S, Iwamoto T, Hirawa N, Kihara M, Takagi N, Ishii M. Identification and characterization of adenosine A₁ receptor–cAMP system in human glomeruli. Kidney Int. 1993;43:928–932. [PubMed] [Google Scholar]
• Traynor T, Yang T, Huang YG, Arend L, Oliverio MI, Coffman T, Briggs JP, Schnermann J. Inhibition of adenosine-1 receptor-mediated preglomerular vasoconstriction in AT1A receptor-deficient mice. Am J Physiol. 1998;275:F922–F927. [PubMed] [Google Scholar]
• Vallon V. P2 receptors in the regulation of renal transport mechanisms. Am J Physiol Renal Physiol. 2008;294:F10–F27. [PubMed] [Google Scholar]
• Vallon V, Richter K, Huang DY, Rieg T, Schnermann J. Functional consequences at the single-nephron level of the lack of adenosine A₁ receptors and tubuloglomerular feedback in mice. Pflugers Arch. 2004;448:214–221. [PubMed] [Google Scholar]
• Vallon V, Muhlbauer B, Osswald H. Adenosine and kidney function. Physiol Rev. 2006;86:901–940. [PubMed] [Google Scholar]
• Vallon V, Miracle C, Thomson S. Adenosine and kidney function: potential implications in patients with heart failure. Eur J Heart Fail. 2008;10:176–187. [PMC free article] [PubMed] [Google Scholar]
• van-Buren M, Bijlsma JA, Boer P, van-Rijn HJ, Koomans HA. Natriuretic and hypotensive effect of adenosine-1 blockade in essential hypertension. Hypertension. 1993;22:728–734. [PubMed] [Google Scholar]
• Wagner C, de Wit C, Kurtz L, Grunberger C, Kurtz A, Schweda F. Connexin40 is essential for the pressure control of renin synthesis and secretion. Circ Res. 2007;100:556–563. [PubMed] [Google Scholar]
• Weaver DR, Reppert SM. Adenosine receptor gene expression in rat kidney. Am J Physiol. 1992;263:F991–F995. [PubMed] [Google Scholar]
• Weihprecht H, Lorenz JN, Schnermann J, Skott O, Briggs JP. Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus. J Clin Invest. 1990;85:1622–1628. [PMC free article] [PubMed] [Google Scholar]
• Weihprecht H, Lorenz JN, Briggs JP, Schnermann J. Vasomotor effects of purinergic agonists in isolated rabbit afferent arterioles. Am J Physiol. 1992;263:F1026–F1033. [PubMed] [Google Scholar]
• Weihprecht H, Lorenz JN, Briggs JP, Schnermann J. Synergistic effects of angiotensin and adenosine in the renal microvasculature. Am J Physiol. 1994;266:F227–F239. [PubMed] [Google Scholar]
• Welch WJ. Adenosine A₁ receptor antagonists in the kidney: effects in fluid-retaining disorders. Curr Opin Pharmacol. 2002;2:165–170. [PubMed] [Google Scholar]
• Wilcox CS, Welch WJ, Schreiner GF, Belardinelli L. Natriuretic and diuretic actions of a highly selective adenosine A₁ receptor antagonist. J Am Soc Nephrol. 1999;10:714–720. [PubMed] [Google Scholar]
• Yagil Y. Interaction of adenosine with vasopressin in the inner medullary collecting duct. Am J Physiol. 1990;259:F679–F687. [PubMed] [Google Scholar]
• Yagil C, Katni G, Yagil Y. The effects of adenosine on transepithelial resistance and sodium uptake in the inner medullary collecting duct. Pflügers Arch. 1994;427:225–232. [PubMed] [Google Scholar]
• Yao K, Kusaka H, Sato K, Karasawa A. Protective effects of KW-3902, a novel adenosine A₁-receptor antagonist, against gentamicin-induced acute renal failure in rats. Jpn J Pharmacol. 1994;65:167–170. [PubMed] [Google Scholar]
• Yao K, Heyne N, Erley CM, Risler T, Osswald H. The selective adenosine A₁ receptor antagonist KW-3902 prevents radiocontrast media-induced nephropathy in rats with chronic nitric oxide deficiency. Eur J Pharmacol. 2001;414:99–104. [PubMed] [Google Scholar]
• Yaoita H, Ito O, Arima S, Endo Y, Takeuchi K, Omata K, Ito S. Effect of adenosine on isolated afferent arterioles. Nippon Jinzo Gakkai Shi. 1999;41:697–703. [PubMed] [Google Scholar]
• Yates MS, Bowmer CJ, Kellett R, Collis MG. Effect of 8-phenyltheophylline, enprofylline and hydrochlorothiazide on glycerol-induced acute renal failure in the rat. J Pharm Pharmacol. 1987;39:803–808. [PubMed] [Google Scholar]
• Zou AP, Nithipatikom K, Li PL, Cowley AW., Jr Role of renal medullary adenosine in the control of blood flow and sodium excretion. Am J Physiol. 1999;45:R790–R798. [PubMed] [Google Scholar]