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

Abstract We investigated the effects of angiotensin I (4×10 −9 , 4×10 −8 and 4×10 −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 (4×10 −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 (1×10 −9 , 1×10 −8 and 1×10 −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 (1×10 −8 and 1×10 −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 (1×10 −7 m ) of angiotensin II throughout reperfusion compared with controls 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.