Estrogen and Enalapril attenuate the Development of Right Ventricular Hypertrophy induced by Monocrotaline in Ovariectomized Rats.
10.3346/jkms.2003.18.5.641
- Author:
Byung Hoon AHN
1
;
Hwan Ki PARK
;
Hyun Gug CHO
;
Hae Ahm LEE
;
Young Man LEE
;
Eun Kyoung YANG
;
Won Jung LEE
Author Information
1. Department of Physiology, School of Medicine, Kyungpook National University, Daegu, Korea. wjleek@knu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Sex Difference;
Cardiac Remodeling, Ventricular;
Hypertension, Pulmonary;
Renin-Angiotensin System
- MeSH:
Angiotensin-Converting Enzyme Inhibitors/pharmacology;
Angiotensinogen/biosynthesis;
Animals;
Body Weight/drug effects;
Densitometry;
Disease Progression;
Enalapril/*pharmacology;
Endothelin-1/biosynthesis;
Estrogens/*pharmacology;
Female;
Hypertrophy, Right Ventricular/chemically induced/*drug therapy;
Male;
Microscopy, Electron;
Monocrotaline/*pharmacology;
Ovariectomy;
RNA/metabolism;
RNA, Messenger/metabolism;
Rats;
Rats, Sprague-Dawley;
Renin/biosynthesis;
Reverse Transcriptase Polymerase Chain Reaction;
Sex Factors;
Support, Non-U.S. Gov't;
Transforming Growth Factor beta/biosynthesis;
Ventricular Remodeling
- From:Journal of Korean Medical Science
2003;18(5):641-648
- CountryRepublic of Korea
- Language:English
-
Abstract:
The present study evaluated the importance of ovarian functions and the renin-angiotensin 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 elevated renin mRNA levels. Gene expression levels of angiotensinogen, TGF-beta1, and endothelin-1 in the hypertrophied RV also increased, but to the less degree than did the renin mRNA. To investigate beneficial effects of estrogen or enalapril on progression of the pulmonary hypertension and RV hypertrophy, histological changes of the lung and heart were examined. Sham-MCT female rats showed histological changes indicating pulmonary hypertension without RV hypertrophy. In contrast, Ovx-MCT rats showed marked RV hypertrophy with pathological changes, denoting severe pulmonary and myocardial injuries. Estrogen-or enalapril-treated Ovx-MCT rats did not show RV hypertrophy, and showed remarkably ameliorated ultrastructural changes in the lung and RV. These results from this rat model suggest that both estrogen and inhibition of the renin-angiotensin system have protective functions against the development of the pulmonary hypertension and cardiac remodeling.