Gene expression of endothelin-1 and endothelin receptor A on monocrotaline-induced pulmonary hypertension in rats after bosentan treatment

Kyoung Ah Lim, Kwan Chang Kim, Min Sun Cho, Bo En Lee, Hae Soon Kim, Young Mi Hong

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18 Scopus citations

Abstract

Background and Objectives: Endothelin (ET)-1, a potent endothelium-derived vasoconstrictor peptide, has a potential pathophysiologic role in pulmonary hypertension. Bosentan, a dual ET receptor (ETA/ETB) antagonist, is efficacious in treatment of pulmonary hypertension. The objectives of this study were to investigate the expression of ET-1 and ET receptor A (ERA) genes and to evaluate the effect of bosentan in monocrotaline (MCT)-induced pulmonary hypertension. Materials and Methods: Four-week-old male Sprague-Dawley rats were treated as follows: control (n=36), subcutaneous (sc) injection of saline; MCT (n=36), sc injection of MCT (60 mg/kg); and bosentan (n=36), sc injection of MCT (60 mg/kg) plus 25 mg/kg/ day bosentan orally. Results: Serum ET-1 concentrations in the MCT group were higher than the control group on day 28 and 42. Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan group on day 28 and 42. In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on day 14,28 and 42. The levels of ET-1 and ERA gene expression were significantly increased in the MCT group compared with control group on day 5, and bosentan decreased the expression of ET-1 on day 5. Conclusion: ET-1 contributes to the progression of cardiopulmonary pathology in rats with MCT-induced pulmonary hypertension. Administration of bosentan reduced ET-1 gene expression in MCT-induced pulmonary hypertension in rats.

Original languageEnglish
Pages (from-to)459-464
Number of pages6
JournalKorean Circulation Journal
Volume40
Issue number9
DOIs
StatePublished - Sep 2010

Keywords

  • Bosentan
  • Endothelin
  • Gene expression
  • Monocrotaline
  • Pulmonary hypertension

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