Adenosine A(1) receptor antagonist KW-3902 prevents hypoxia-induced renal vasoconstriction

Abstract

Studies were carried out to determine the intrarenal adenosine production during hypoxia, and the protective effects of a selective adenosine A(1) receptor antagonist 8-(noradamantan-3-yl)-1, 3-dipropylxanthine (KW-3902) on hypoxia-induced renal hemodynamic changes. We used an in vivo microdialysis method and measured the renal interstitial concentration of adenosine in response to hypoxic exposure in anesthetized mechanically ventilated rabbits. Normocapnic systemic hypoxia (PaO(2) = 32 +/- 6 mm Hg) caused a significant decrease in renal blood flow and increase in renal vascular resistance, indicating a renal vasoconstriction. The basal interstitial concentration of adenosine in the cortex was 293 +/- 70 nM, which was significantly higher than that in the medulla (170 +/- 23 nM). Five minutes after beginning hypoxia, the renal interstitial concentration of adenosine approximately tripled in the cortex and doubled in the medulla. During treatment with KW-3902, hypoxemia caused a similar increase in the adenosine concentration compared with that in the absence of KW-3902. The administration of KW-3902, however, significantly attenuated hypoxia-induced reduction in renal blood flow. These results suggest that adenosine was involved in hypoxia-induced renal vasoconstriction via its effects on adenosine A(1) receptors, and that KW-3902 had a partial protective effect against renal vasoconstriction during hypoxemia.