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.