Estrogen and Enalapril attenuate the Development of Right Ventricular Hypertrophy induced by Monocrotaline in Ovariectomized Rats

Abstract

INTRODUCTIONGender differences in the development of cardiovascular diseases have been documented in both human and animal studies. The rate of incidence of cardiovascular disease is lower in premenopausal women than in men, but increases sharply in postmenopausal women (1). Among the clinical consequences of postmenopausal estrogen deficiency, the deaths associated with cardiovascular diseases represent the largest concern in public health. Many studies have demonstrated that estrogen replacement therapy reduces the risk of cardiovascular disease in postmenopausal women (2). Animal studies also demonstrate gender differences in the development of cardiovascular diseases (3-5). Thus, circulating endogenous estrogen is proposed to protect against cardiovascular disease. However, mechanisms by which estrogen induces its protective effects are not fully understood.Various vasoactive substances and growth factors have been implicated in cardiac and vascular remodeling, as well as further degenerative transformation of these tissues (6). A critical role of the cardiac renin-angiotensin system (RAS), among others, has been recognized (7,8). Increased activity of the cardiac RAS has been confirmed both in humans (9) and animal models of cardiac failure (10, 11), whereas inhibition of the RAS decreased ventricular remodeling and improved cardiac function (12, 13).Cardiac hypertrophy is known to be one of the most critical risk factors of heart diseases. It has been demonstrated that monocrotaline (MCT) treatment produces pulmonary hypertension and right ventricular (RV) hypertrophy in male rats but not in female rats (4, 14). We previously found enhanced gene expressions of the cardiac RAS in the hypertrophied RV of male rats (15). The present study evaluated 1) the importance of the ovairan function and the RAS in the progression of the pulmonary hypertension, and 2) RV hypertrophy in MCT treated rats. We examined the cardiac expression of genes that contribute to the pathogenesis of cardiac hypertrophy, such as the RAS components, TGF-1, and endothelin-1 as well as histological changes in the lung and heart. Although this MCT rat model has no human equivalent, as a study design, we used a system of MCT-induced cardiopulmonary dysfunction to investigate possible beneficial effects of estrogen and inhibition of angiotensin converting enzyme. J Korean Med Sci 2003; 18: 641-8 ISSN 1011-8934 Copyright � The Korean Academy of Medical Sciences 641 Estrogen and Enalapril attenuate the Development of Right Ventricular Hypertrophy induced by Monocrotaline in Ovariectomized RatsThe present study evaluated the importance of ovarian functions and the reninangiotensin system in the progression of the right ventricular (RV) hypertrophy. Female Sprague-Dawley rats were bilaterally ovariectomized (Ovx) and injected with monocrotaline (MCT, 60 mg/kg, sc). Four weeks after MCT-treatment, only the male and Ovx female rats showed marked RV hypertrophy. The hypertrophied RV of the male-MCT and Ovx-MCT rats exhibited remarkably elevate...

Inhibitory effect of ginsenoside Rb1 on cardiac hypertrophy induced by monocrotaline in rat

“…In the present study, we used MCT-induced RVH in rat to probe the possible inhibitory effect of Rb 1 on cardiac hypertrophy, because it has been well known that MCT is converted in the liver to MCT-pyrrole which causes injury of the lung vasculature and leads to pulmonary hypertension and RVH (Chen et al, 2001;Ahn et al, 2003). In MCT-treated animals, the significant increase in LW/BW, RVHI, and RV/BW, the electron microscopic findings of RV, and the elevation of ANP expression (a fetal heart marker protein) strongly suggested that there existed the formation of pulmonary hypertension and RVH, which meant that the establishment of RVH model in our experiment was successful.…”

Moderate Pulmonary Arterial Hypertension in Male Mice Lacking the Vasoactive Intestinal Peptide Gene

“…In a study of mice with deletion of the endothelial nitric oxide synthase gene, structural evidence of pulmonary hypertension was evident in male but not in female adult mice. 29 Further investigation of gender differences in the expression of the PAH phenotype in VIP Ϫ/Ϫ mice and of the possible role of estrogen in such differences 30,31 is clearly in order. A predominant expression of the pulmonary vascular abnormalities in male VIP Ϫ/Ϫ mice, if confirmed, would be clearly different from human IPAH, which is more prevalent in women.…”

Total Ginsenosides Inhibit the Right Ventricular Hypertrophy Induced by Monocrotaline in Rats

“…16,17) In the present study, we used MCT-induced RVH in rat to examine the possible inhibitory effect of TG on cardiac hypertrophy. In MCT-treated animals, the increase in RVPSP and the findings in the electron microscopic observation strongly indicated that there existed the formation of pulmonary hypertension.…”