Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

Vijayakumar Sukumaran, Kenichi Watanabe, Punniyakoti T. Veeraveedu, Rajarajan A. Thandavarayan, Narasimman Gurusamy, Meilei Ma, Ken'Ichi Yamaguchi, Kenji Suzuki, Makoto Kodama, Yoshifusa Aizawa

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Multiple trials over the past several years have examined indications for angiotensin receptor blockers (ARBs) in the treatment of left ventricular (LV) dysfunction, both acutely after myocardial infarction and in chronic heart failure (CHF). However, the effects of telmisartan, an ARB in rats with CHF after experimental autoimmune myocarditis (EAM) have not yet been analyzed. CHF was elicited in Lewis rats by immunization with cardiac myosin, and 28 days after immunization, the surviving Lewis rats were divided into two groups and treated with either telmisartan (10 mg kg-1 day-1) or vehicle. After 4 weeks of treatment, we analyzed the effects of telmisartan on cardiac function, proinflammatory cytokines and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by telmisartan treatment in rats with CHF compared with those of vehicle-treated rats with CHF. Telmisartan significantly reduced levels of cardiac fibrosis, hypertrophy and its marker molecules (LV mRNA expressions of transforming growth factor beta 1, collagen I and III, and atrial natriuretic peptide), and peroxisome proliferator-activated receptor-γ protein expression compared with those of vehicle-treated rats. CHF-induced increases in myocardial mRNA expressions of proinflammatory cytokines, (interleukin (IL)-6, IL-1Β), monocyte chemoattractant protein-1 and matrix metalloproteinases (MMP-2 and-9) were also suppressed by the treatment with telmisartan. Moreover, the plasma level of angiotensin-II was significantly elevated in telmisartan-treated rats. Our results indicate that telmisartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

Original languageEnglish (US)
Pages (from-to)695-702
Number of pages8
JournalHypertension Research
Volume33
Issue number7
DOIs
StatePublished - Jul 2010

Keywords

  • PPAR-γ
  • chronic heart failure
  • cytokine
  • myocardial fibrosis

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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