Cardiac effects of angiotensin I and angiotensin II: Dose-response studies in the isolated perfused rat heart

We investigated the effects of angiotensin I (4 x 10^-9, 4 x 10^-8 and 4 x 10^-7 M) on myocardial contractility, heart rate and coronary perfusion in the isolated rat heart before and after inhibition of angiotensin-converting enzyme (ACE) by captopril (4 x 10^-4 M). We also studied the post-ischaemic recovery of cardiac function in isolated hearts subjected to global myocardial ischaemia and reperfused with various doses of angiotensin II (1 x 10^-9, 1 x 10^-8 and 1 x 10^-7 M). Angiotensin I significantly reduced coronary flow, the vasoconstrictor effect of a second identical dose was attenuated after inhibition of ACE with captopril. Angiotensin II reduced coronary flow to the same extent as angiotensin I at a concentration four times lower. Left ventricular developed pressure was reduced by angiotensin I and angiotensin II in a dose-dependent manner. Heart rate was not affected by angiotensin I and was significantly lowered by the highest doses (1 x 10^-8 and 1 x 10^-7 M) of angiotensin II. Post-ischaemic recoveries of vascular and contractile function were similar in control hearts and in hearts given angiotensin II during reperfusion. However, left ventricular end-diastolic pressure was increased by the highest dose (1 x 10^-7 M) of angiotensin II throughout reperfusion compared with control, or hearts receiving lower doses (NS). In conclusion the attenuated vasoconstrictor response to angiotensin I after captopril pre-treatment confirms the existence of an intracardiac renin-angiotensin system operative in vitro. Our results also suggest that angiotensin II, at a high concentration, may play a negative role in relaxation in the ischaemic-reperfused injured heart.