Response to Sympathetic Nerve Stimulation and Noradrenaline in Atria Treated With Reserpine and in Atria From Rabbits Pretreated With Reserpine

Abstract

It is widely known that cardiac noradrenaline is markedly depleted by pretreat ment 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 reten tion 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 in hibits 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 appli ed in vitro on the chronotropic response of isolated atria to sympathetic nerve stimu lation, tyramine and exogenous noradrenaline, (b) modification of the contractile ten sion-frequency relationship and of the chronotropic and inotropic effects of noradrena line by pretreatment of animals with reserpine, and (c) effects of treatment with nor adrenaline or dopamine in the presence of monoamine oxidase inhibitor on the chrono tropic response of atria from reserpine-pretreated rabbits to tyramine and to sympathetic nerve stimulation. METHODSStudies were carried out on 43 albino rabbits of either sex, weighing 1.8 to 2.2. kg.

Effects of reserpine on nerve stimulation‐induced constrictions in canine isolated splenic artery

“…It is generally accepted that the intragranular pool is a functional or available NA storage site that is more readily released by nerve impulses 17,18 . Those conclusions are supported by observations in isolated atria from reserpine‐treated guinea‐pigs, rabbits and cats that show that refilling of the NA stores restores responses of the atrial pacemaker to tyramine, but not to sympathetic nerve stimulation 19,21 . In contrast with those reports, we found that not only tyramine‐induced, but also nerve stimulation‐induced adrenergic responses were consistently restored after replenishment of NA, as demonstrated previously in the guinea‐pig vas deferens 22 and cat nictitating membrane 23 .…”

The Pharmacology of Rauwolfia Alkaloids

“…Inhibition of monoamine oxidase does not affect the failure of noradrenaline to restore responses in rabbit atria (TODA et al, 1970).…”