Studies on the Interaction Between Angiotensin and the Sympathetic Nervous System

Abstract

The interactions between angiotensin and the sympathetic nervous system in the mammalian cardiovascular system have been studied. In the isolated central artery from the rabbit ear, the constrictor action of angiotensin was enhanced in the presence of endogenous noradrenaline but unaltered by exogenous noradrenaline. In pithed rats, the responses to each of three procedures causing the release of noradrenaline from sympathetic nerve endings were increased by angiotensin. The responses to injected noradrenaline were unaltered by angiotensin. The possible significance of these results is discussed. Using a technique developed from existing methods, the action of a variety of drugs on the cardiovascular system of bonsbious cats has been studied. It was shown that the extent of the pressor effect of angiotensin was determined, in part, by the noradrenaline content of the neuronal stores. The responses were reduced by depletion of noradrenaline and restored when the stores were replenished. The responses to angiotensin were increased after inhibition of monoamine oxidase. The role of endogenous noradrenaline in the pressor responses to angiotensin remains uncertain but is independent of postsynaptic adrenergic receptor sites. A series of metal ion chelating agents have been examined for specific anti-angiotensin activity. Of these, only sodium diethyl-dithiocarbamate possessed specific anti-angiotensin activity. This could be readily demonstrated in vivified rats, but in anesthetized cats, it was complicated by the ability of sodium diethyldithiocarbamate to potentiate the responses to noradrenaline and therefore to potentiate the adrenal medullary component of the angiotensin response. The failure of the other chelating agents to block the pressor responses to angiotensin suggests that sodium diethyl-dithiocarbamate may act independently of metal chelation. It is suggested that sodium diethyl-dithiocarbamate might be a suitable prototype from which to develop a specific anti-angiotensin agent. No such agent exists at present, and its discovery might facilitate investigations into the role of the renin-angiotensin system.