Action of Angiotensin and Analogues on the Heart

The action of angiotensin II (AT II ) 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.AT II , heptapeptide (2–8), and 1-Sar-AT II increase the amplitude of contraction and prolong the P–R interval of the electrocardiogram. High doses of AT II and heptapeptide (2–8), but not of 1-Sar-AT II , decrease heart rate. Inhibitory analogues (8-Gly-AT II , 1-Sar,8-Gly-AT II ) 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 AT II , heptapeptide (2–8) and 1-Sar-AT II , while antagonists do not produce any change. The plateau phase of ventricular cells is similarly prolonged by AT II and heptapeptide (2–8); the other analogues were not tested.Hearts taken from reserpinized rabbits respond to AT II and heptapeptide (2–8) with similar changes of tension and transmembrane potential as the hearts of non-treated rabbits.The effects of AT II and heptapeptide (2–8) are inhibited by relatively small doses of 8-Gly-AT II and 1-Sar,8-Gly-AT II ; inhibition by 8-Gly-AT II is surmountable with AT II .The results indicate that (a) AT II and heptapeptide (2–8) have a direct effect on the myocardium, (b) this effect is antagonized by position 8 substituted analogues of AT II that inhibit the action of AT II 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.