Endothelin-a receptor antagonist prevents and reverses chronic
hypoxia-induced pulmonary hypertension in the rat.
Dicarlo, Vick S., Shi-Juan Chen, Qing Cheng Meng, Joan Durand, Mitsuo
Yano, Yiu-Fai Chen, and Suzanne Oparil.
Vascular Biology and Hypertension Program, Division of
Cardiovascular Disease, Department of Medicine, and [acute]aDivision
of Neonatology, Department of Pediatrics, University of Alabama at
Birmingham School of Medicine, Birmingham, Alabama 35294 Tsukuba
Research Institute, Banyu Pharmaceutical Co., Ltd., Tsukuba, Techno
-Park Oho, Okubo 3, Tsukuba 300-33, Japan
APStracts 2:0120L, 1995.
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 m) 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 l/h 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 wk of hypoxia. BQ-123
infusion instituted prior to 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 ET-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.
Received 1 February 1995; accepted in final form 21 June 1995.
APS Manuscript Number L33-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.