Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats

J Appl Physiol (1985). 1995 Dec;79(6):2122-31. doi: 10.1152/jappl.1995.79.6.2122.


The current study examined the effects of bosentan, an orally active antagonist of endothelin-A and -B receptors, on the development and maintenance of hypoxia (10% O2)-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with bosentan (100 mg.kg-1.day-1, 1 gavage/day for 2 days) completely blocked the pulmonary vasoconstrictor response to acute hypoxia. Chronic bosentan treatment (100 mg.kg-1.day-1 po in the food) instituted 48 h before hypoxic exposure prevented the subsequent development of pulmonary hypertension, attenuated the associated right heart hypertrophy, and prevented the remodeling of small (50-100 microns) pulmonary arteries without altering systemic arterial pressure. Institution of bosentan treatment (for 4 wk) after 2 wk of hypoxia produced a significant reversal of established hypoxia-induced pulmonary hypertension (from 36 +/- 1 to 25 +/- 1 mmHg), right heart hypertrophy, and pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous endothelin-1 plays a major role in hypoxic pulmonary vasoconstriction and/or hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that endothelin-receptor blockade may be useful in the treatment of hypoxic pulmonary hypertension humans.

Publication types

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

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Bosentan
  • Heart Rate / drug effects
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / prevention & control*
  • Hypoxia / drug therapy*
  • Hypoxia / prevention & control*
  • Male
  • Pulmonary Circulation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology*
  • Time Factors


  • Sulfonamides
  • Bosentan