ETA-receptor antagonist prevents and reverses chronic hypoxia-induced pulmonary hypertension in rat.

Academic Article

Abstract

  • The selective endothelin-A (ETA)-receptor antagonist BQ-123 has been shown to prevent chronic hypoxia-induced pulmonary hypertension in the rat. Therefore in the current study we utilized BQ-123 to test the hypothesis that blockade of the ETA receptor can reverse as well as prevent the increase in mean pulmonary artery pressure, right ventricle-to-left ventricle plus septum ratio, and percent wall thickness in small (50-100 microns) pulmonary arteries observed in male Sprague-Dawley rats exposed to normobaric hypoxia (10% O2, 2 wk). Infusion of BQ-123 (0.4 mg.0.5 microliter-1.h-1 for 2 wk in 10% O2) begun after 2 wk of hypoxia significantly reversed the established pulmonary hypertension and prevented further progression of right ventricular hypertrophy during the third and fourth week of hypoxia. BQ-123 infusion instituted before exposure to hypoxia completely prevented the hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular remodeling. These findings suggest that, in the lung, hypoxia induced an increase synthesis of endothelin-1, which acts locally on ETA receptors to cause pulmonary hypertension, right heart hypertrophy, and pulmonary vascular remodeling, while ETA-receptor blockade can both prevent and reverse these processes.
  • Authors

    Published In

    Keywords

  • Animals, Cardiomegaly, Chronic Disease, Endothelin Receptor Antagonists, Hypertension, Pulmonary, Hypoxia, Infusions, Intravenous, Male, Peptides, Cyclic, Rats, Rats, Sprague-Dawley
  • Digital Object Identifier (doi)

    Author List

  • DiCarlo VS; Chen SJ; Meng QC; Durand J; Yano M; Chen YF; Oparil S
  • Start Page

  • L690
  • End Page

  • L697
  • Volume

  • 269
  • Issue

  • 5 Pt 1