Captopril Attenuates Matrix Metalloproteinase-2 and -9 in Monocrotaline-Induced Right Ventricular Hypertrophy in Rats

Abstract

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.

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

“…anesthesia using SONOS 5500 (Hewlett-Packard Co., Andover, MA, USA) with a dynamically focused S12 probe (5 -12 MHz, Hewlett Packard Co.) as described previously (13). Acceleration time (AT) and ejection time (ET) were measured from pulsed Doppler of pulmonary artery flow velocity.…”

“…The ventricular tissues for histological examinations were fixed in 10% neutral buffered formalin for histological examination. Thin paraffin sections (2 μm) were made and Azan staining was performed by a standard procedure (13).…”

“…Western blot analysis was performed as described previously (13). Briefly, RV samples were homogenized in lysis buffer [20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 1 mM EDTA-2Na, 1 mM EGTA, 1% Triton, 2.5 mM sodium pyrophosphate, 1 mM β-glycerophosphate, 1 mM Na 3 VO 4 , 1 mg/ ml leupeptin; Cell Signaling Technology, Inc., Danvers, MA, USA] containing 1% protease inhibitor cocktail (Nacalai Tesque, Inc., Kyoto) and centrifuged.…”

“…We previously reported that an angiotensin-converting enzyme (ACE) inhibitor, captopril, attenuates monocrotaline-induced RV hypertrophy, fibrosis, dysfunction, and MMP-2 and MMP-9 expressions in rats (13). Therefore, it is assumed that RAS promotes the development of monocrotalineinduced RV remodeling.…”

Efeito de um programa de exercício físico em portador da Síndrome Marfan com disfunção ventricular

“…ACE inhibitors promote the cardiac anti-remodeling effect, mainly when administered in the early stages of post-AMI. These effects may be secondary to the reduction in neurohumoral activity, anti-ischemic effect and reduction of matrix metalloproteinases 2 and 9, factors that either isolated or in combination, contribute to the occurrence of cardiac hypertrophy 8 .…”