Coronary and Myocardial Actions of Angiotensin

In the dog heart-lung preparation, single injections of 40 µg angiotensin II produced consistently a biphasic response. Initial impairment of cardiac function was observed with decrease of cardiac output and of ventricular force, and with increase of atrial pressures. After 10 to 20 seconds, there was a positive inotropic effect, with an increase of cardiac output and of ventricular force, and a decrease in atrial pressures. Responses were comparable in reserpinized and nonreserpinized preparations. Tachyphylaxis to angiotensin was found consistently in the heart-lung preparation, with a regular decrease in response following second and third injections. A positive inotropic action of angiotensin II was demonstrated in the cat papillary muscle preparation. These studies demonstrated that angiotensin has a direct cardiac action, namely a positive inotropic effect. This action probably does not depend upon myocardial stores of catecholamines. When the left anterior descending coronary artery of the dog was perfused with blood at a constant flow, single intracoronary injections of angiotensin (1.0 µg) consistently increased coronary resistance (6% to 92%). Continuous intracoronary infusion of angiotensin increased coronary vascular resistance when blood concentrations were as low as 0.42 µg/ liter. No evidence of initial cardiac depression or of increased coronary vascular resistance was found after norepinephrine. It is concluded that the initial impairment of cardiac performance following angiotensin is caused at least in part by decreased coronary blood flow. Caution is suggested in the use of angiotensin in the treatment of human shock because of its action upon the coronary circulation.