Synthetic angiotensin a has pronounced inotropic effects on isometrically contracting, isolated papillary muscles of kittens. The response increases with drug concentration over the range from 10-10 M to 10-5 M. The mean maximum increase in tension development is 120%. Contractility is raised by angiotensin through an increase in the degree of activation of the contractile elements with no significant change in the duration of their active state. Low concentrations of angiotensin have a greater inotropic action than equimolar concentrations of l-norepinephrine; but the maximum inotropic effect obtainable with l-norepinephrine is almost twice that of angiotensin.
The inotropic effects of angiotensin on cat atrial muscle are slight, and the drug is inactive on frog ventricular myocardium. It has no effect on the resting length-tension relationship of mammalian atrial or ventricular muscle. The frequency of impulse formation in the SA node is not significantly changed by concentrations of angiotensin up to 10-5 M. In marked contrast to levarterenol, angiotensin does not cause ectopic impulse formation in atrial or ventricular muscle.
It is suggested that the positive inotropic effect of angiotensin on ventricular myocardium is of importance for the pressor action of the drug in the intact circulation. The increase in myocardial contractility tends to minimize or prevent decreases in cardiac output in the face of increased resistance to cardiac ejection and thus supports the elevation of arterial pressure.
- Received September 24, 1963.
- © 1964 American Heart Association, Inc.