TY - JOUR
T1 - Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy
AU - Sukumaran, Vijayakumar
AU - Watanabe, Kenichi
AU - Veeraveedu, Punniyakoti T.
AU - Thandavarayan, Rajarajan A.
AU - Gurusamy, Narasimman
AU - Ma, Meilei
AU - Yamaguchi, Ken'Ichi
AU - Suzuki, Kenji
AU - Kodama, Makoto
AU - Aizawa, Yoshifusa
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - PPAR-γ
KW - chronic heart failure
KW - cytokine
KW - myocardial fibrosis
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U2 - 10.1038/hr.2010.67
DO - 10.1038/hr.2010.67
M3 - Article
C2 - 20535115
AN - SCOPUS:77954379820
SN - 0916-9636
VL - 33
SP - 695
EP - 702
JO - Hypertension Research
JF - Hypertension Research
IS - 7
ER -