BQ123, an ETA-receptor antagonist, attenuates hypoxic pulmonary hypertension in rats
Bonvallet, S.T.; Zamora, M.R.; Hasunuma, K.; Sato, K.; Hanasato, N.; Anderson, D.; Sato, K.; Stelzner, T.J.
American Journal of Physiology 266(4 Pt 2): H1327-H1331
1994
ISSN/ISBN: 0002-9513 PMID: 8184910 Document Number: 431158
To investigate the role of endothelin-1 (ET-1) in the pathogenesis of hypoxic pulmonary hypertension, we studied the effects of a recently described endothelin-receptor antagonist (ET-A), BQ123, on the development of this process. Intraperitoneal osmotic pumps were placed into 8-wk-old Sprague-Dawley rats that received either saline or BQ123 (0.15 mg/h). The rats were maintained in room air normoxia or placed in a hypobaric chamber (380 Torr) for 2 wk to induce hypoxic pulmonary hypertension. There were no hemodynamic differences between normoxic rats treated with either saline or BQ123. However, treatment with BQ123 attenuated the hypoxia-induced increase in pulmonary arterial mean pressure and total pulmonary resistance index by 60 and 87% respectively. There was also a reduction in hypoxia-induced right ventricular hypertrophy in the BQ123 group. Histological studies performed using a barium-gelatin fixation technique in hypoxic BQ123-treated animals demonstrated a decrease in medial wall thickness in arteries corresponding to the respiratory and terminal bronchioles, respectively. Similarly, there was a significant reduction in the degree of muscularization of more distal vessels at the level of alveolar ducts in BQ123-treated hypoxic rats, We conclude that the ET-A-receptor antagonist BQ123 attenuates the development of hypoxic pulmonary hypertension in rats in vivo, thereby suggesting a possible contributing role for ET-1 and the ET-A receptor in the pathogenesis of this process.