All issues > Volume 52(6); 2009

Original Article

Korean J Pediatr. 2009;52(6):689-695. Published online June 15, 2009.

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

Kyoung Ah KA Lim¹, Jung Yun JY Shim¹, Sang Ho SH Cho¹, Kwan Chang KC Kim³, Jae Jin JJ Han³, Young Mi YM 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

Correspondence Young Mi YM 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.

Keywords :Endothelin receptor antagonist, Monocrotaline, Pulmonary hypertension