The Mode of Action of Angiotensin

Abstract

The contractile action of angiotensin upon smooth muscle preparations has been studied to try and elucidate the mechanism of action of angiotensin. To distinguish between the primary interaction of angiotensin with the smooth muscle cells and the resulting contraction, responses to acetylcholine were also measured. On guinea-pig ileum, angiotensin responses were found to be more susceptible to metabolic inhibition than acetylcholine responses and this suggested that the angiotensin response might involve an energy dependent step. In further experiments it was shown that this energy dependent mechanism was associated with the direct component of angiotensin's action in this tissue. However, the existence of an indirect, cholinergic mechanism was a complicating factor and the investigation was therefore extended to rat descending colon and rat uterus where the action of angiotensin was wholly direct. Conditions which had revealed the energy dependent mechanism on guinea~pig ileum failed to affect these preparations and the use of more severe conditions produced an equal reduction of responses to acetylcholine and angiotensin, the magnitude of which varied from tissue to tissue- A study of the carbohydrate metabolism of these tissues revealed differences both between tissues and during the course of the oestrous cycle which explained the observed variation in tissue responses during metabolic inhibition. The energy dependence of the angiotensin response was demonstrated by the use of 2,4-dinitrophenol, a more specific metabolic inhibitor, and this confirmed that energy was required for the direct interaction of the hormone with the smooth muscle cells. The possible role of a mediator in this action of angiotensin was investigated but from preliminary experiments, it appeared that neither cyclic AMP nor prostaglandins were involved. Although the nature of the energy dependent mechanism has not been elucidated it seems that it may involve the movement of inorganic ions. These findings are related to a possible mechanism of action for angiotensin.