Myocardial salvaging effect of telmisartan in experimental model of myocardial infarction

• Published in: European journal of pharmacology Vol. 619; no. 1; pp. 75 - 84
• Main Authors: Goyal, Sameer, Arora, Sachin, Mittal, Rajan, Joshi, Sujata, Nag, Tapas C., Ray, Ruma, Kumari, Santosh, Arya, Dharamvir Singh
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.10.2009; Elsevier
• Subjects: Angiotensin II receptor blocker; Animals; Benzimidazoles - pharmacology; Benzimidazoles - therapeutic use; Benzoates - pharmacology; Benzoates - therapeutic use; Biological and medical sciences; Biomarkers - metabolism; Body Weight - drug effects; Cardiology. Vascular system; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Catalase - metabolism; Coronary heart disease; Disease Models, Animal; Heart; Heart - drug effects; Heart - physiopathology; Isoproterenol - pharmacology; L-Lactate Dehydrogenase - metabolism; Lipid Peroxidation - drug effects; Male; Medical sciences; Myocardial infarction; Myocardial Infarction - chemically induced; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Myocardium - pathology; Oxidative stress; Pharmacology. Drug treatments; PPAR-γ (peroxisome proliferator-activated receptor-gamma); Rats; Rats, Wistar; Superoxide Dismutase - metabolism; Telmisartan; Myocardial infarction; Oxidative stress; Angiotensin II receptor blocker; Telmisartan; PPAR-γ (peroxisome proliferator-activated receptor-gamma); Imidazole derivatives; Angiotensin II receptor; Peptide hormone; Cardiovascular disease; PPAR-γ receptor; Coronary heart disease; Myocardial disease; Octapeptide; Renin angiotensin system; Benzimidazole derivatives; Myocardium; Antihypertensive agent; Sartan derivatives; Models; Circulatory system; Angiotensin antagonist; Angiotensin II
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.07.026

Telmisartan is a unique angiotensin II receptor blocker with an additional peroxisome proliferator-activated receptor-gamma (PPAR-γ) 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 10 mg/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 10 mg/kg produced more pronounced protective effects than the other two doses (1 and 5 mg/kg body weight). Present study thus provides evidence for protective effects of telmisartan on myocardium in experimentally induced myocardial infarction.