Angiotensin II reduces infarct size and has no effect on post‐ischaemic contractile dysfunction in isolated rat hearts

• Published in: British journal of pharmacology Vol. 134; no. 1; pp. 38 - 45
• Main Authors: Ford, William R, Clanachan, Alexander S, Robin Hiley, C, Jugdutt, Bodh I
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2001; Nature Publishing
• Subjects: Angiotensin II; Angiotensin II - pharmacology; Animals; Biological and medical sciences; Blood Pressure - drug effects; Cardiology. Vascular system; Coronary Circulation - drug effects; Coronary heart disease; Dose-Response Relationship, Drug; Heart; Heart - drug effects; Heart - physiopathology; Heart Rate - drug effects; Heart Ventricles - drug effects; Heart Ventricles - physiopathology; In Vitro Techniques; ischaemia‐reperfusion injury; Langendorff perfusion; Male; Medical sciences; Myocardial Contraction - drug effects; myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocardial Ischemia - physiopathology; Perfusion; Rats; Rats, Sprague-Dawley; working heart perfusion; Infarct; Peptides; Pathophysiology; Rat; Rodentia; Cardioprotective agent; Contractility; Cardiovascular disease; Coronary heart disease; Myocardial disease; In vitro; Biological activity; Vascular disease; Vertebrata; Mammalia; Reperfusion; Ischemia; Animal; Myocardium; Antiïschemic; Angiotensin II; Mechanism of action
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704225

In order to test the hypothesis that angiotensin II exacerbates myocardial ischaemia‐reperfusion (IR) injury, we examined the effects of graded angiotension II concentrations of angiotensin II on IR injury in both working and non‐working (Langendorff) isolated rat hearts.
Non‐working hearts were subjected to 30 min aerobic perfusion (baseline) then 25 min of global, no‐flow ischaemia followed by 30 min of reperfusion either in the absence (control, n=7) or presence of 1 (n=6) or 10 nM (n=5) angiotensin II). Recoveries of LV developed pressure and coronary flow after 30 min reperfusion in control hearts (58±9 and 40±8% of baseline levels, respectively) were no different from hearts treated with 1 or 10 nM angiotensin II. Infarct size (determined at the end of reperfusion by triphenyltetrazolium chloride staining) was reduced by angiotensin II in a concentration‐dependent manner (from a control value of 27±3 to 18±4% and 9±3% of the LV, respectively).
Working hearts were subjected to 50 min pre‐ischaemic (pre‐I) aerobic perfusion then 30 min of global, no‐flow ischaemia followed by 30 min of reperfusion either in the absence (control, n=14) or presence of 1 (n=8), 10 (n=7) or 100 nM (n=7) angiotensin II). In controls, post‐ischaemic (post‐I) left ventricular (LV) work and efficiency of oxygen consumption were depressed (43±9 and 42±10% of pre‐I levels, respectively). The presence of angiotensin II throughout IR had no effect on LV work compared with control.
Thus, angiotensin II reduces infarct size in a concentration‐dependent manner but has no effect on contractile stunning associated with IR in isolated rat hearts.
British Journal of Pharmacology (2001) 134, 38–45; doi:10.1038/sj.bjp.0704225