| Summary: | 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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