Abstract
It is widely known that cardiac noradrenaline is markedly depleted by pretreatment of animals with reserpine (1) but only slightly reduced by treatment of the isolated heart with reserpine (2, 3). Pretreatment of animals with reserpine depresses the retention of exogenous noradrenaline in the heart (4) by reducing the uptake of the amine by storage granules (5) and by increasing the destruction of the amine by monoamine oxidase in sympathetic nerve terminals (6). Reserpine when applied in vitro significantly inhibits the uptake of the amine by the isolated heart (7). Reserpine is shown to disappear almost completely from the body in a few hours when injected intravenously (8) but when applied in vitro it acts directly on the heart until the drug is washed out repeatedly. Modification by reserpine of the cardiac functions and the responsiveness of the isolated heart to endogenous and exogeneous noradrenaline would be attributed to the marked depletion of cardiac noradrenaline, the inhibition of the amine uptake by the heart and/ or the actions of reserpine per se. Although the positive chronotropic response of the heart to sympathetic nerve stimulation and to indirectly-acting sympathomimetic amines is markedly reduced and the response to noradrenaline is enhanced by pretreatment with reserpine, little is known about the effects of reserpine applied in vitro on the responses to endogenous and exogeneous noradrenaline.
The present investigation was undertaken to examine (a) effects of reserpine applied in vitro on the chronotropic response of isolated atria to sympathetic nerve stimulation, tyramine and exogenous noradrenaline, (b) modification of the contractile tension-frequency relationship and of the chronotropic and inotropic effects of noradrenaline by pretreatment of animals with reserpine, and (c) effects of treatment with noradrenaline or dopamine in the presence of monoamine oxidase inhibitor on the chronotropic response of atria from reserpine-pretreated rabbits to tyramine and to sympathetic nerve stimulation.
