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 pathophysiological conditions. Their effects are brought about by activation of membrane bound P1- and P2-purinoceptors located on smooth muscle and endothelial cells. In this study we analyzed the purinoceptor mediated 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 perfused with medium containing indomethacin. After preconstriction, drug induced changes in the vessel diameters were measured by a photoelectric device.
RESULTS: ATP (EC50 = 1 mumol/liter), added intraluminally, caused maximal vasodilation of 80 to 100% of the preconstriction response in both species. This effect was inhibited by the P1-purinoceptor antagonist 8-p-(sulphophenyl)theophylline (100 mumol/liter), suggesting that it was in part due to breakdown of ATP to adenosine. The nature of purinoceptor mediated renal vasodilation was studied further in rabbit renal arteries. Adenosine (EC50 = 1 mumol/liter) as well as the P2Y-receptor agonists ADP beta S (EC50 = 0.4 mumol/liter) and 2-MeSATP (EC50 = 0.2 mumol/liter) dilated the arteries by 80 to 100%. The effects of 2-MeSATP, which were to a much lesser extent that of ADP beta S but not that of adenosine, were attenuated by the P2Y-antagonist reactive blue 2 (3 mumol/liter). Removal of the endothelium almost abolished the vasodilation induced by adenosine and ATP. In contrast, these dilator response were only slightly attenuated by the nitric oxide synthase blockers NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine (300 mumol/liter each), whereas acetylcholine and 2-MeSATP induced dilation was markedly reduced by NG-nitro-L-arginine methyl ester.
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 induced 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, adenosine.