MECHANISM OF THE INHIBITORY ACTION OF GUANETHIDINE ON CARDIOVASCULAR RESPONSES TO TYRAMINE AND AMPHETAMINE

¹ Department of Pharmacoloqy and Toxicology, University of Wisconsin, Madison, Wisconsin

The influence of guanethidine on responses of the blood pressure and isolated, atropinized atria of rats to tyramine and amphetamine was studied. Administration of guanethidine to animals anesthetized with urethane produced hypotension, inhibited the pressor actions of tyramine and amphetamine, and potentiated the response to norepinephrine. At this time, catecholamine concentrations in the heart were not significantly altered. Isolated atria also failed to exhibit the usual cardiostimulant responses to tyramine and amphetamine after exposure to guanethidine in the absence of any reduction in their concentrations of catecholamines. Atria from rats whose cardiac catecholamines were depleted by guanethidine did not respond to tyramine or amphetamine. The effects of these amines were restored by incubation of the atria with norepinephrine. Depletion of cardiac catecholamines by guanethidine was prevented by TM-10 (2,6-xylyl choline ether bromide) but not by cocaine. It is suggested that guanethidine may affect the action of sympathomimetic amines in two ways: 1) by inhibiting the release of normal stores of catecholamines by the sympathomimetic amines, an acute effect, and 2) by depleting the tissues of their stores of catecholamines, a delayed effect.