Pharmacological characterization of the renovascular P2 purinergic receptors

Isolated rat kidneys, perfused at a constant flow with a nonrecirculated medium, were used to investigate the effects of P2 purinergic receptor agonists on renal vascular resistance. A potent P2y agonist, 2-methylthio ATP, dilated the kidney in a concentration-dependent manner, a response that was similar to that elicited by acetylcholine. The vasodilator responses to 2-methylthio ATP and to acetylcholine were nearly abolished by N omega-nitro-/-arginine methyl ester, an antagonist of nitric oxide formation by endothelial cells. A potent P2x agonist, alpha, beta-methylene ATP, constricted the kidney in a concentration-dependent manner, and the effect was potentiated by N omega-nitro-/-arginine methyl ester. This latter finding suggests that alpha,beta-methylene ATP activates P2y receptors, but with such a low potency that any tendency for vasodilation is masked by the predominant P2x receptor-induced constriction. Collectively, the results indicate the renal vasculature can either constrict or dilate in response to P2 purinergic receptor agonists, depending upon which subclass of receptor is activated, P2x (constrict) or P2y (dilate). Furthermore, the P2y receptor-induced vasodilation appears to be mediated by endothelial cell nitric oxide formation.