Abstract

The effects of the purines, adenosine 5'-triphosphate (ATP) and guanosine 5'-triphosphate (GTP), and the pyrimidines, uridine 5'-triphosphate (UTP), cytidine 5'-triphosphate (CTP), and thymidine 5'-triphosphate (TTP), on vascular resistance were investigated in the rat mesenteric arterial bed. In preparations at basal tone, these agents produced dose-related vasoconstriction with a potency order of ATP greater than CTP greater than UTP much greater than TTP = GTP. When tone was raised with norepinephrine (30 microM), these agents caused dose-related vasodilatation with the potency order of UTP = ATP greater than TTP = GTP. CTP did not elicit vasodilatation. Removal of the endothelium with sodium deoxycholate resulted in an increased responsiveness of the mesenteric bed preparation to the vasoconstrictor effects of each of the purines and pyrimidines tested. The selective P2 X-purinoceptor-desensitizing agent alpha,beta-methylene ATP inhibited vasoconstrictor responses to ATP and to CTP but had no effect on vasoconstrictor responses elicited by UTP, TTP, and GTP. In raised-tone preparations, vasodilator responses to ATP, UTP, TTP, and GTP were abolished after removal of the endothelium with sodium deoxycholate. Responses to acetylcholine were also abolished; those to sodium nitroprusside were unimpaired. An inhibitor of the formation of nitric oxide from L-arginine, N omega-nitro-L-arginine methyl ester (30 microM), which antagonizes responses mediated by endothelium-derived relaxing factor (nitric oxide), attenuated vasodilatation to ATP, UTP, and acetylcholine but not to sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)