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BQ123, an ETA-receptor antagonist, attenuates hypoxic pulmonary hypertension in rats.

Abstract
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 (ETA), 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 ETA-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 ETA receptor in the pathogenesis of this process.
AuthorsS T Bonvallet, M R Zamora, K Hasunuma, K Sato, N Hanasato, D Anderson, K Sato, T J Stelzner
JournalThe American journal of physiology (Am J Physiol) Vol. 266 Issue 4 Pt 2 Pg. H1327-31 (Apr 1994) ISSN: 0002-9513 [Print] United States
PMID8184910 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Endothelin Receptor Antagonists
  • Peptides, Cyclic
  • cyclo(Trp-Asp-Pro-Val-Leu)
Topics
  • Animals
  • Blood Vessels (drug effects, pathology)
  • Endothelin Receptor Antagonists
  • Hemodynamics (drug effects)
  • Hypertension, Pulmonary (etiology, pathology, physiopathology)
  • Hypoxia (complications)
  • Male
  • Peptides, Cyclic (pharmacology)
  • Pulmonary Circulation (drug effects)
  • Rats
  • Rats, Sprague-Dawley

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