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 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.
Traquandi
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Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Riva
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D000803:Angiotensin I / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril