Reduction of infarct size by orally administered des-aspartate-angiotensin I in the ischemic reperfused rat heart.
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.
Wen
Qiang
Q
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Building MD2, 18 Medical Drive, Singapore 117597, Singapore.
Sim
Meng-Kwoon
MK
Tang
Feng-Ru
FR
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
D002317:Cardiovascular Agents; D011453:Prostaglandins; D000803:Angiotensin I; D007213:Indomethacin