Myocardial salvaging effect of telmisartan in experimental model of myocardial infarction.
Telmisartan is a unique angiotensin II receptor blocker with an additional peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activity. The present study has been designed to investigate whether telmisartan treatment attenuates the development of acute myocardial infarction in isoproterenol-treated rats by restoring hemodynamic, biochemical, histopathological and ultrastructural changes. Isoproterenol-induced cardiotoxicity was evidenced by marked decrease in systolic, diastolic, mean arterial pressures, maximal positive rate of developed left ventricular pressure (+LVdP/dt(max), a marker of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dt(max), a marker of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load). In addition, a significant reduction in activities of myocardial creatine kinase-MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) level along with increase in malondialdehyde (MDA) content were observed. Oral pretreatment with telmisartan (1, 5 and 10mg/kg body weight) daily for a period of 14 days, favourably modulated the studied parameters in isoproterenol-induced myocardial injury. In addition, the protective role of telmisartan on isoproterenol-induced myocardial damage was further confirmed by histopathological and ultrastructural examinations. Telmisartan at a dose of 10mg/kg produced more pronounced protective effects than the other two doses (1 and 5mg/kg body weight). Present study thus provides evidence for protective effects of telmisartan on myocardium in experimentally induced myocardial infarction.
Goyal
Sameer
S
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi-110029, India.
Arora
Sachin
S
Mittal
Rajan
R
Joshi
Sujata
S
Nag
Tapas C
TC
Ray
Ruma
R
Kumari
Santosh
S
Arya
Dharamvir Singh
DS
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D000077333:Telmisartan
D001562:Benzimidazoles; D001565:Benzoates; D015415:Biomarkers; D002316:Cardiotonic Agents; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D007545:Isoproterenol; D000077333:Telmisartan