UBC Theses and Dissertations
Possible role of adenosine 5’-triphosphate in the cardiovascular system of the rat Poon, Christina I.
The experiments described in this thesis were designed to characterize a possible role for adenosine 5’-triphosphate (ATP) in the cardiovascular system of the conscious rat. This study assessed the role of ATP in the control of mean arterial pressure (MAP), heart rate (HR), and mean circulatory filling pressure (MCFP) by examining the effects of receptor antagonists (of cx-adrenoceptors, P1- andP2-purinoceptors, and autonomic ganglia), chemi cal sympathectomy (by reserpine or guanethidine), and ATP per se. Furthermore, we compared the contribution of endogenous ATP and noradrenaline (NA) in basal vascular tone with that during drug-induced vasodilatation and concomittant elevation of sympa thetic nerve activity. Phentolamine (non-selective c-adrenoceptor antagonist) was found to be a more effective arterial than venous vasodilator in both basal conditions and during drug (hydralazine or nifedipine)-induced vasodilatation and reflex venoconstriction. While MCFP was not significantly decreased by phentolamine either under basal conditions or during hydralazine treatment, phentolamine did decrease MCFP in the presence of nifedipine. Following suramin treatment, the phentolamine-induced depressor effect was significantly potentiated whereas MCFP remained unchanged. Under basal conditions, mecamylamine very effectively reduced both MAP and MCFP whereas in the presence of hydralazine induced vasodilatation and elevated venomotor tone, ganglion blockade reduced MCFP but not MAP. Blockade ofP2-purinoceptors by suramin produced a dose-dependent increase in MAP and decrease in HR neither of which was affected by hydralazine, nifedipine, mecamylamine, reserpine, or guanethidine. Suramin failed to reduce MCFP in the pres ence of hydralazine, nifedipine, or guanethidine. In contrast, mecamylamine treatment revealed a significant dose-dependent decrease in MCFP by suramin, while reserpine treatment revealed a slight but significant decline in MCFP. l.v. infusion of ATP produced profound depressor and bradycardic effects. The ATP induced depressor effect was unaffected by mecamylamine and suramin whereas block ade of Pi-purinoceptors by 8-phenyltheophylline clearly and significantly attenuated this response. Blockade of P2y-purinoceptors by cibacron blue only slightly and insignificantly attenuated the depressor effect of ATP. ATP-induced bradycardia was not affected by mecamylamine or cibacron blue whereas 8-phenyltheophylline completely abolished this response and even revealed a slight, but insignificant, increase in HR in response toATP. Suramin slightly but insignificantly enhanced the ATP-induced bradycardia. ATP produced a slight but insignificant depression of MCFP which was unaltered in the presence of suramin, and slightly but insignificantly enhanced both during mecamylamine-induced ganglion blockade and following 8-phenyltheophylline treatment. Cibacron blue, in con trast, revealed a slight but insignificant ATP-induced increase in MCFP.
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