J Korean Med Sci.
2003 Oct;18(5):641-648. 10.3346/jkms.2003.18.5.641.
Estrogen and Enalapril attenuate the Development of Right Ventricular Hypertrophy induced by Monocrotaline in Ovariectomized Rats
- Affiliations
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- 1Department of Physiology, School of Medicine, Kyungpook National University, Daegu, Korea. wjleek@knu.ac.kr
- 2Department of Otolaryngology, College of Medicine Keimyung University, Daegu, Korea.
- 3Department of Visual Optics, Kyungwoon University, Gumi, Korea.
- 4Department of Physiology, School of Medicine, Catholic University of Daegu, Daegu, Korea.
- KMID: 1130032
- DOI: http://doi.org/10.3346/jkms.2003.18.5.641
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.
Keyword
MeSH Terms
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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
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