Effects of Telmisartan on Right Ventricular Remodeling Induced by Monocrotaline in Rats

Abstract

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.

Effects of Captopril and Telmisartan on Matrix Metalloproteinase-2 and -9 Expressions and Development of Left Ventricular Fibrosis Induced by Isoprenaline in Rats

“…11,12) In the present study, captopril and telmisartan could not suppress isoprenaline-induced myocardial fibrosis and MMPs expressions. There are several reasons for this difference.…”

“…12) Briefly, LV tissues were homogenized in lysis buffer (20 mM Tris-HCl pH 7.5, 150 mM NaCl, 1 mM ethylenediaminetetraacetic acid (EDTA)-2Na, 1 mM ethylene glycol bis(2-aminoethylether)-N,N,NЈ,NЈ-tetraacetic acid (EGTA), 1% Triton, 2.5 mM sodium pyrophosphate, 1 mM b-glycerophosphate, 1 mM Na 3 VO 4 , 1 mg/ml leupeptin; Cell Signaling Technology Inc., Danvers, MA, U.S.A.) containing 1% protease inhibitor cocktail (Nacalai Tesque Inc.) and centrifuged. The supernatant was used for Western blotting.…”

Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

“…Pre-clinical studies using different models of PAH and right heart failure, however confirmed that the use of ACE inhibitors or angiotensin blockers significantly reduces RV remodelling and improves cardiac function and/or survival [66][67][68][69]. We conclude that in PAH, pharmacological interference in RAAS could (partially) reverse pulmonary and cardiac remodelling, which warrants a prospective controlled clinical study of the effects of ACE inhibitors, angiotensin blockers and/or aldosterone antagonists.…”

Evaluation of Right Ventricle by Speckle Tracking and Conventional Echocardiography in Rats With Right Ventricular Heart Failure

“…[8][9][10] A total of 26 rats aged 10-weeks weighing 310 -360 g were randomly assigned to two groups. RVHF rats (n = 14) received a 60 mg/ kg subcutaneous injection of MCT and the control rats (n = 12) a subcutaneous injection of vehicle.…”