Renal vascular reactivity to P-2-purinoceptor activation in spontaneously hypertensive rats

This study was performed to determine the possible contribution of an imbal ance between P-2X (vasoconstriction) and P-2Y (vasodilation)-purinergic rea ctivity to the increased vascular resistance of spontaneously hypertensive rats (SHR). The vasoactive responses to alpha,beta-methylene ATP and 2-meth ylthio ATP specific agonists, respectively, for P2X and P2Y purinergic rece ptors were characterized in isolated perfused kidneys from Wistar Kyoto (WK Y) and SHR. To analyze P-2X- and P-2Y-purinergic reactivity we used phenyle phrine and barium chloride, or acethylcholine (ACh) and sodium nitroprussid e (NP) as reference compounds, respectively. The renal vasculature from SHR showed markedly enhanced reactivity to alpha,beta-methylene ATP, phenyleph rine and barium chloride. The dose-response curves were characterized by a similar threshold, with a greater maximal response. There were no significa nt differences in the dose-response curves or in maximal vasodilation to 2- methylthio ATP, ACh or NP when both groups were compared, except at the dos e of 10(-6) g/g kidney weight of NP in which the SHR group showed an increa sed responsiveness. The results indicate that the increased responsive ness of kidneys from SHR to alpha,beta-methylene ATP may be due to nonspecific functional changes in the renal vasculature rather than to a specific alter ation in the activity of renal P-2X-purinoceptors. Our results also indicat e that P-2Y-purinergic reactivity, nitric oxide-induced vasodilation and th e cGMP-dependent mechanisms of vasodilation are well preserved in SHR. Copy right (C) 2000 S. Karger AG, Basel.