Nature of the Inotropic Action of Angiotensin on Ventricular Myocardium

The effect of changes in various chemical and physical factors on the positive inotropic action of angiotensin was studied in isolated papillary muscles of kittens. Pretreatment of the animals with reserpine did not diminish the positive inotropic effect of angiotensin. Concentrations of nethalide which strongly antagonize the response of the papillary muscle to levarterenol or tyramine had no effect on the inotropic concentration-effect curve for angiotensin. It is concluded that angiotensin does not release significant amounts of cate-cholamines from the cardiac stores and that its inotropic action on ventricular myocardium does not result from stimulation of adrenergic β-receptors. Increases in external calcium concentration, decreases in sodium concentration, and shortening of the interval between contractions diminish both the absolute and the relative inotropic effect of angiotensin. All these maneuvers and angiotensin itself raise myocardial contractility by increasing the degree of activation of the contractile element. Cooling of papillary muscles does not decrease the absolute inotropic effect of the drug. Angiotensin and increases in external calcium concentration affect the mechanical properties of papillary muscles in a similar fashion. Angiotensin may raise contractility by augmenting the entry of Ca ++ into the myocardial fiber.