title: Effects of telmisartan on right ventricular remodeling induced by monocrotaline in rats.
abstract: The present study investigated whether telmisartan, an angiotensin II type 1 receptor antagonist, has cardioprotective effects on monocrotaline-induced right ventricular (RV) remodeling in rats. Six-week-old male Wistar rats were divided into control group (CONT), monocrotaline (60 mg/kg, i.p.)-treated group (MCT), monocrotaline (60 mg/kg, i.p.) + telmisartan (3 mg/kg per day, p.o.)-treated group (MCT+TEL), and telmisartan (3 mg/kg per day, p.o.) alone-treated group (TEL). Hearts were excised after echocardiography examinations at day 25. Significant increase in RV weight and histologically remarkable fibrosis in RV sections were observed in MCT. Tricuspid annular plane systolic excursion, a parameter for RV systolic function, significantly decreased in MCT. These RV hypertrophy, fibrosis, and dysfunction were inhibited in MCT+TEL. In MCT, the acceleration time/ejection time ratio of pulmonary artery flow velocity, an index of pulmonary hypertension, significantly decreased. This decrease was not affected in MCT+TEL. In MCT, expressions and activities of matrix metalloproteinase (MMP)-2 and MMP-9, which play a critical role in cardiac remodeling, significantly increased in the RV. In MCT+TEL, these increases in expressions and activities were inhibited. MCT showed about 2-fold increase in transforming growth factor-beta1 expression compared with CONT, and such an increase was not decreased in MCT+TEL. There were no significant changes of these parameters in TEL compared with CONT. These results suggest that telmisartan could attenuate the monocrotaline-induced RV remodeling through improvements of RV hypertrophy, fibrosis, dysfunction, and inhibition of MMPs.
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan. mokada@vmas.kitasato-u.ac.jp
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Okada
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Harada
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kikuzuki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hara
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004452:Echocardiography; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016686:Monocrotaline / Q000494:pharmacology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D053773:Transforming Growth Factor beta1; D016686:Monocrotaline; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077333:Telmisartan