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Comparative effects of aspirin with ACE inhibitor or angiotensin receptor blocker on myocardial infarction and vascular function
Bo-qing Zhu
Cardiology Research, VA Medical Center, University of California, San Francisco, USA
Richard E Sievers
Division of Cardiology, Department of Medicine, University of California
Amanda EM Browne
Division of Cardiology, Department of Medicine, University of California
Randall J Lee
Division of Cardiology, Department of Medicine, University of California
Kanu Chatterjee
Division of Cardiology, Department of Medicine, University of California
William Grossman
Division of Cardiology, Department of Medicine, University of California, parmley{at}medicine.ucsf.edu
Joel S Karliner
Cardiology Research, VA Medical Center, University of California, San Francisco, USA
William W Parmley
Division of Cardiology, Department of Medicine, University of California
Objectives
We previously showed that an angiotensin-converting enzyme inhibitor (captopril) or an angiotensin receptor blocker (losartan) reduced infarct size and improved endothelial function in a rat model of ischaemia-reperfusion. The present study was undertaken to see if aspirin (ASA) antagonised the beneficial effects of captopril or losartan.
Methods
One hundred and fourteen Sprague-Dawley rats were randomised into six groups; Control, ASA, captopril, losartan, ASA+captopril, and ASA+losartan. ASA, captopril or losartan were given at a concentration of 40 mg/kg/day in drinking water. After six weeks of pre-treatment, the rats were subjected to 17 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion, with haemodynamic and ECG monitoring. During the reperfusion period, the effective refractory period (ERP), ventricular fibrillation threshold (VFT) and bleeding time (BT) were measured. In fresh aortic rings precontracted with phenylephrine, endothelium-dependent and -independent relaxations were assessed using
acetylcholine and nitroglycerin. Results
Haemodynamic changes were not different between the groups. Serum ASA concentrations were 0.5, 1.1 and 0.6 mg/dl in the ASA, ASA+captopril and ASA+losartan groups, respectively, and BT was prolonged (p<0.01). ASA alone reduced endothelium-dependent relaxation (-29±8 vs. -69±11%, p<0.01), but did not change endothelium-independent relaxation. ASA did not affect endothelial relaxation induced by acetylcholine in the presence of either captopril or losartan. Angiotensin I and ERP were elevated by captopril and losartan. Angiotensin II and VFT were elevated by losartan. ASA with captopril, captopril and losartan equally reduced infarct size, compared with control (39±3, 39±4 and 39±5 vs. 53±3%, all p<0.05).
Conclusions
Captopril and losartan had similar cardiovascular protective effects in a rat model of ischaemia-reperfusion. Aspirin did not attenuate the cardiovascular protective effects of captopril or losartan.
Key Words: myocardial infarct size • ischaemia-reperfusion • aspirin • ACE inhibitor • angiotensin II receptor blocker • endothelial function
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Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 1,
31-37 (2003)
DOI: 10.3317/jraas.2003.005
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