title: Comparative effects of aspirin with ACE inhibitor or angiotensin receptor blocker on myocardial infarction and vascular function.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Cardiology Research, VA Medical Center, University of California, San Francisco, 94143-0124, USA. parmley@medicine.ucsf.edu
authors.forename: Bo-qing
authors.initials: BQ
authors.lastname: Zhu
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.forename: Amanda E M
authors.initials: AE
authors.lastname: Browne
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Kanu
authors.initials: K
authors.lastname: Chatterjee
authors.forename: William
authors.initials: W
authors.lastname: Grossman
authors.forename: Joel S
authors.initials: JS
authors.lastname: Karliner
authors.forename: William W
authors.initials: WW
authors.lastname: Parmley
mesh_terms: D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000494:pharmacology*; D001241:Aspirin / Q000097:blood / Q000494:pharmacology*; D001760:Bleeding Time; D002216:Captopril / Q000494:pharmacology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006439:Hemodynamics; D019808:Losartan / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000473:pathology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D019808:Losartan; D001241:Aspirin