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Valsartan, an Angiotensin II Receptor Blocker, Attenuates Cardiac Dysfunction and Oxidative Stress in Isoproterenol-Induced Cardiotoxicity.
MedLine Citation:
PMID:  21380857     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Valsartan has significant blood pressure lowering effect via modulating renin-angiotensin system although its mechanism of action in isoproterenol (ISO)-induced myocardial injury is largely unknown. We therefore evaluated the effect of valsartan in ISO-induced oxidative stress and cardiotoxicity during β-adrenergic receptor stimulation in rats. ISO (85 mg/kg, s.c.) was administered on thirteenth and fourteenth day for induction of cardiotoxicity. ISO-treated rats showed significant decrease (P < 0.01) in mean arterial pressure (70.2 ± 9.11 vs. 104.86 ± 8.93), maximal positive (1601.3 ± 338.87 vs. 2789.16 ± 301.76), and negative (1495.76 ± 151.78 vs. 2039.6 ± 279.1) rate of developed left ventricular pressure and increase in left ventricular end-diastolic pressure (5.81 ± 0.51 vs. 2.37 ± 0.43) as compared to the sham group. Similarly, significant reduction in CK-MB (91.42 ± 5.88 vs. 142.63 ± 6.9), LDH (50.52 ± 5.18 vs. 73.28 ± 4.29) levels, and anti-oxidant enzymes activities were observed. Valsartan (15, 30, and 60 mg/kg/day, p.o.) pretreatment for 14 days favorably modulated these altered parameters. However, valsartan (60 mg/kg) only showed significant improvement (P < 0.01) in cardiac dysfunction, myocardial injury markers, and anti-oxidant status of myocardium in ISO-induced cardiotoxicity. Histopathology and ultrastructural studies further validated the protective effect of valsartan (60 mg/kg). Altogether, these results suggest that cardioprotective effect of valsartan is mediated through augmenting endogenous anti-oxidant defense system, preserving hemodynamic function and structural integrity of myocardium.
Authors:
Sameer Goyal; Saurabh Bharti; Kanhei Charan Sahoo; Ashok Kumar Sharma; Dharamvir Singh Arya
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-6
Journal Detail:
Title:  Cardiovascular toxicology     Volume:  -     ISSN:  1559-0259     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101135818     Medline TA:  Cardiovasc Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cardiovascular Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.
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