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Effect of endothelin receptor blockade on monocrotaline-induced pulmonary hypertension in rats

Korean Journal of Pediatrics 2009;52(6):689-695.
Published online June 15, 2009.
Effect of endothelin receptor blockade on monocrotaline-induced pulmonary hypertension in rats
Kyoung Ah Lim1, Jung Yun Shim1, Sang Ho Cho1, Kwan Chang Kim3, Jae Jin Han3, Young Mi Hong2
1Department of Pediatrics, College of Medicine, Pochon CHA University
2Department of Pediatrics, School of Medicine, Ewha Womans University, Seoul, Korea
3Department of Thoracic and Cardiovascular Surgery, School of Medicine, Ewha Womans University, Seoul, Korea
Monocrotaline으로 유발한 백서 폐동맥 고혈압에서 Endothelin 수용체 차단제 투여의 효과
임경아1, 심정연1, 조상호1, 김관창3, 한재진3, 홍영미2
1포천중문의과대학 소아청소년과
2이화여자대학교 의과대학 소아과학교실
3이화여자대학교 의과대학 흉부외과학교실
Correspondence: 
Young Mi Hong, Email: hongym@chollian.net
Abstract
Purpose
: To examine the effect of bosentan, a dual endothelin receptor (ER) antagonist, on the development of monocrotaline (MCT)-induced pulmonary hypertension in rats by especially focusing on the pulmonary vascular morphology changes.
Methods
: Sprague-Dawley rats were treated as follows: controls received a subcutaneous saline injection, MCT-treated rats received a subcutaneous MCT injection, and bosentan-treated rats received a MCT injection followed by treatment with bosentan (20 mg/kg/day). To assess the effects of ER blockade on the time course, the animals were exsanguinated, and their hearts and lungs were dissected after 7, 14, or 28 days.
Results
: The mean body weights of the MCT- and bosentan-treated rats were significantly lower than that of the control rats on days 7, 14, and 28. Bosentan administration significantly inhibited the progression of right ventricular hypertrophy on day 28 (right ventricle/[left ventricle+septum]: 0.71±0.10 in MCT-treated rats vs. 0.49±0.09 in bosentan-treated rats; P<0.05). Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan-treated rats on day 28 (49.96±10.06% in MCT-treated rats vs. 47.09±10.48% in bosentan-treated rats; P<0.05). In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on days 14 and 28.
Conclusion
: Bosentan administration in intermediate doses exerts inhibitory effects on lung vascular hypertrophy and right ventricular hypertrophy during the development of MCT-induced pulmonary hypertension in rats.
Key Words: Endothelin receptor antagonist, Monocrotaline, Pulmonary hypertension


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