PURINOCEPTORS MEDIATE RENAL VASODILATION BY NITRIC-OXIDE DEPENDENT AND INDEPENDENT MECHANISMS

Background. Adenosine triphosphate (ATP) and its metabolites including adenosine modulate renal vascular tone under physiological and pathop hysiological conditions, Their effects are brought about by activation of membrane bound P-1- and P-2- purinoceptors located on smooth muscl e and endothelial cells. In this study we analyzed the purinoceptor me diated dilation of rabbit and human renal arteries, and evaluated the possible involvement of endothelium-derived relaxing factors. Methods. Segments of rabbit and human renal arteries were incubated and perfus ed with medium containing indomethacin. After preconstriction, drug in duced changes in the vessel diameters were measured by a photoelectric device. Results. ATP (EC50 = 1 mu mol/liter), added intraluminally, c aused maximal vasodilation of 80 to 100% of the preconstriction respon se in both species. This effect was inhibited by the P1-purinoceptor a ntagonist 8-p-(sulphophenyl)theophylline (100 mu mol/liter), suggestin g that it was in part due to breakdown of ATP to adenosine. The nature of purinoceptor mediated renal vasodilation was studied further in ra bbit renal arteries. Adenosine (EC50 = 1 mu mol/liter) as well as the P2Y-receptor agonists ADP beta S (EC50 = 0.4 mu mol/liter) and 2-MeSAT P (EC50 = 0.2 mu mol/liter) dilated the arteries by 80 to 100%. The ef fects of 2-MeSATP, which were to a much lesser extent that of ADP beta S but not that of adenosine, were attentuated by the P2Y-antagonist r eactive blue 2 (3 mu mol/liter). Removal of the endothelium almost abo lished the vasodilation induced by adenosine and ATP. In contrast, the se dilator responses were only slightly attenuated by the nitric oxide synthase blockers N-G-nitro-L-arginine methyl ester and N-G-nitro-L-a rginine (300 mu mol/liter each), whereas acetylcholine and 2-MeSATP in duced dilation was markedly reduced by N-G-nitro-L-arginine methyl est er. Conclusions. P1-purinoceptors activated by adenosine dilate rabbit renal arteries by an endothelium-derived relaxing factor that appears to be distinct from nitric oxide. In contrast, P2Y-purinoceptor induc ed renal dilation is mediated by nitric oxide. ATP, the physiological activator of P2Y-purinoceptors, is rapidly broken down to adenosine in rabbit and human renal arteries. Therefore, in rabbit and human renal arteries the vasodilatory effect of exogenous ATP mainly results from P1-purinoceptor activation probably through its breakdown product, ad enosine.