title: Reduction of infarct size by orally administered des-aspartate-angiotensin I in the ischemic reperfused rat heart.
abstract: Occlusion of the left main coronary artery for 45 min caused sizable infarct scarring of the left ventricular wall in the rat heart at 14 days post-reperfusion. Daily oral administration of des-aspartate-angiotensin I (DAA-I) for 14 days attenuated the area of the infarct scar and transmurality. The attenuation was dose-dependent and biphasic; maximum effective dose was 1524 nmol/kg, and doses higher than this were progressively inactive. The exact mechanism of the biphasic attenuation is not known, and receptor down-regulation by internalization, which has been implicated in a similar biphasic nature for the anticardiac hypertrophic action of DAA-I, could be a likely cause. Indomethacin (101 micromol/kg, i.p.), administered sequentially after the daily oral dose of DAA-I (1524 nmol/kg), completely inhibited the attenuation at 14 days post-reperfusion, indicating that prostaglandins may be involved in transducing the attenuation. The present findings support earlier indications that DAA-I exerts protective actions in cardiovascular pathologies in which angiotensin II is implicated. It is suggested that DAA-I exerts the cardioprotective action by acting on the same indomethacin-sensitive angiotensin AT1 receptor. Although similar array of protective actions are also seen with another endogenous angiotensin, angiotensin-(1-7), the present findings demonstrate for the first time the ability of an endogenous angiotensin to reduce the infarct size of an ischemic-reperfusion injured rat heart.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National University of Singapore, Building MD2, 18 Medical Drive, Singapore 117597, Singapore.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wen
authors.forename: Meng-Kwoon
authors.initials: MK
authors.lastname: Sim
authors.forename: Feng-Ru
authors.initials: FR
authors.lastname: Tang
mesh_terms: D000284:Administration, Oral; D000803:Angiotensin I / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002317:Cardiovascular Agents; D011453:Prostaglandins; D000803:Angiotensin I; D007213:Indomethacin