Action of Angiotensin and Analogues on the Heart

Abstract

The action of angiotensin II (ATII) and of several analogues, including antagonists, has been studied on isolated perfused rabbit hearts. Changes of transmembrane potential have been recorded from atrial and ventricular fibers with floating microelectrodes.ATII, heptapeptide (2–8), and 1-Sar-ATII increase the amplitude of contraction and prolong the P–R interval of the electrocardiogram. High doses of ATII and heptapeptide (2–8), but not of 1-Sar-ATII, decrease heart rate. Inhibitory analogues (8-Gly-ATII, 1-Sar,8-Gly-ATII) are inactive on tension but prolong slightly the P–R interval.The plateau phase of the action potential (A.P.) in atrial fibers is significantly prolonged by ATII, heptapeptide (2–8) and 1-Sar-ATII, while antagonists do not produce any change. The plateau phase of ventricular cells is similarly prolonged by ATII and heptapeptide (2–8); the other analogues were not tested.Hearts taken from reserpinized rabbits respond to ATII and heptapeptide (2–8) with similar changes of tension and transmembrane potential as the hearts of non-treated rabbits.The effects of ATII and heptapeptide (2–8) are inhibited by relatively small doses of 8-Gly-ATII and 1-Sar,8-Gly-ATII; inhibition by 8-Gly-ATII is surmountable with ATII.The results indicate that (a) ATII and heptapeptide (2–8) have a direct effect on the myocardium, (b) this effect is antagonized by position 8 substituted analogues of ATII that inhibit the action of ATII on smooth muscles and in vivo, and (c) changes of tension of myocardial fibers are accompanied by an increased duration of A.P. plateau phase.