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.
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Authors | S T Bonvallet, M R Zamora, K Hasunuma, K Sato, N Hanasato, D Anderson, K Sato, T J Stelzner |
Journal | The American journal of physiology
(Am J Physiol)
Vol. 266
Issue 4 Pt 2
Pg. H1327-31
(Apr 1994)
ISSN: 0002-9513 [Print] United States |
PMID | 8184910
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Endothelin Receptor Antagonists
- Peptides, Cyclic
- cyclo(Trp-Asp-Pro-Val-Leu)
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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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