PHARMACOLOGICAL CHARACTERIZATION OF THE RENOVASCULAR P2 PURINERGIC RECEPTORS

Isolated rat kidneys, perfused at a constant flow with a nonrecirculat ed medium, were used to investigate the effects Of P2 purinergic recep tor agonists on renal vascular resistance. A potent P2y agonist, 2-met hylthio ATP, dilated the kidney in a concentration-dependent manner, a response that was similar to that elicited by acetylcholine. The vaso dilator responses to 2-methylthio ATP and to acetylcholine were nearly abolished by N(omega)-nitro-l-arginine methyl ester, an antagonist of nitric oxide formation by endothelial cells. A potent P2x agonist, al pha,beta-methyl-ene ATP, constricted the kidney in a concentration-dep endent manner, and the effect was potentiated by N(omega)-nitro-/-argi nine methyl ester. This latter finding suggests that alpha,beta-methyl ene ATP activates P2y receptors, but with such a low potency that any tendency for vasodilation is masked by the predominant P2x receptor-in duced constriction. Collectively, the results indicate the renal vascu lature can either constrict or dilate in response to P2 purinergic rec eptor agonists, depending upon which subclass of receptor is activated , P2x (constrict) or P2y (dilate). Furthermore, the P2y receptor-induc ed vasodilation appears to be mediated by endothelial cell nitric oxid e formation,