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

Am J Physiol. 1995 Nov;269(5 Pt 1):L690-7. doi: 10.1152/ajplung.1995.269.5.L690.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cardiomegaly / etiology
  • Cardiomegaly / pathology
  • Chronic Disease
  • Endothelin Receptor Antagonists*
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / physiopathology*
  • Hypoxia / complications*
  • Infusions, Intravenous
  • Male
  • Peptides, Cyclic / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • Endothelin Receptor Antagonists
  • Peptides, Cyclic
  • cyclo(Trp-Asp-Pro-Val-Leu)