Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy.
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--gamma protein expression compared with those of vehicle-treated rats. CHF-induced increases in myocardial mRNA expressions of proinflammatory cytokines, (interleukin (IL)-6, IL-1beta), 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.
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Vijayakumar
V
Sukumaran
Kenichi
K
Watanabe
Punniyakoti T
PT
Veeraveedu
Rajarajan A
RA
Thandavarayan
Narasimman
N
Gurusamy
Meilei
M
Ma
Ken'ichi
K
Yamaguchi
Kenji
K
Suzuki
Makoto
M
Kodama
Yoshifusa
Y
Aizawa
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis; D005355:Fibrosis; D006333:Heart Failure / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009205:Myocarditis / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D000077333:Telmisartan; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000276:immunology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D016207:Cytokines; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077333:Telmisartan