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.) alonetreated 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-β1 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.

Abstract. Little is known about the influence of angiotensin converting enzyme (ACE) inhibitors on matrix metalloproteinase (MMP) in right ventricular remodeling. We investigated the effect of captopril, an ACE inhibitor, on MMP-2 and MMP-9 in monocrotaline-induced right ventricular hypertrophy. Six-week-old male Wistar rats were injected intraperitoneally with monocrotaline (60 mg/ kg) or saline. The rats were administrated captopril (30 mg / kg per day) or a vehicle orally for 24 days from the day of monocrotaline injection. At day 25, echocardiography was performed and hearts were excised. Expressions and activities of MMP-2 and MMP-9 were measured by Western blotting and by gelatin zymography, respectively. In monocrotalineinjected rats, right ventricular weight / tail length ratio increased significantly. Histological analysis revealed cardiomyocyte hypertrophy and fibrosis in right ventricular sections. Echocardiography showed right ventricular dysfunction compared with saline-injected rats. The right ventricular hypertrophy, fibrosis, and dysfunction were inhibited by captopril. However, captopril did not attenuate an increase in pulmonary artery pressure. MMP-2 and MMP-9 expressions and activities in right ventricles increased significantly in monocrotaline-injected rats and captopril inhibited them. These findings indicate that captopril attenuates the development of monocrotalineinduced right ventricular hypertrophy in association with inhibition of MMP-2 and MMP-9 in rats.