Interaction of the novel inotropic agent, ASL-7022, with alpha and beta adrenoceptors in the cardiovascular system of the pithed rat: comparison with dobutamine and dopamine.
Three selective inotropic agents, ASL-7022, dobutamine and dopamine, were evaluated for their effects at alpha and beta adrenoceptors in the cardiovascular system of the pithed rat. ASL-7022, dobutamine and dopamine were equipotent as pressor agents in propranolol- and reserpine-pretreated pithed rats; however, the mechanisms involved in their alpha adrenoceptor-mediated pressor effects were markedly different. The pressor response of ASL-7022 was mediated entirely by postsynaptic vascular alpha-2 adrenoceptors, whereas the pressor response of dobutamine was mediated exclusively by postsynaptic vascular alpha-1 adrenoceptors. The pressor response of dopamine was mediated by both postsynaptic vascular alpha-1 and alpha-2 adrenoceptors. All three compounds elicited beta-2 adrenoceptor-mediated vasodepressor responses in pithed rats when vascular tone was elevated by a constant infusion of angiotensin II. In contrast to the equal vasopressor potencies of these compounds, the vasodepressor activities varied by more than two orders of magnitude with ASL-7022 being the most potent and dopamine the least potent. Based on ratios of relative potencies for alpha adrenoceptor-mediated vasopressor effects and beta-2 adrenoceptor-mediated vasodepressor effects, it appears that dobutamine possesses an equal balance between its vasopressor and vasodepressor potencies, such that the net effect in the vasculature is a physiological antagonism with little or no change in blood pressure, consistent with clinical observations and experiments in animals. In contrast, the vasopressor potency of dopamine exceeds its potency as a depressor agent, such that the net effect is vasoconstriction, consistent with clinical and animal studies.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D002395:Catecholamines / Q000494:pharmacology*; D003655:Decerebrate State; D004280:Dobutamine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D002316:Cardiotonic Agents; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; C036054:ASL 7022; D004298:Dopamine