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

Studies were carried out to determine the intrarenal adenosine production d uring hypoxia, and the protective effects of a selective adenosine A(1) rec eptor antagonist 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902) on hy poxia-induced renal hemodynamic changes. We used an in vivo microdialysis m ethod and measured the renal interstitial concentration of adenosine in res ponse to hypoxic exposure in anesthetized mechanically ventilated rabbits. Normocapnic systemic hypoxia (PaO2 = 32 +/- 6 mm Hg) caused a significant d ecrease in renal blood flow and increase in renal vascular resistance, indi cating a renal vasoconstriction. The basal interstitial concentration of ad enosine in the cortex was 293 +/- 70 nM, which was significantly higher tha n that in the medulla (170 +/- 23 nM). Five minutes after beginning hypoxia , the renal interstitial concentration of adenosine approximately tripled i n the cortex and doubled in the medulla. During treatment with KW-3902, hyp oxemia caused a similar increase in the adenosine concentration compared wi th that in the absence of KW-3902. The administration of KW-3902, however, significantly attenuated hypoxia-induced reduction in renal blood flow. The se results suggest that adenosine was involved in hypoxia-induced renal vas oconstriction via its effects on adenosine A(1) receptors, and that KW-3902 had a partial protective effect against renal vasoconstriction during hypo xemia.