Importance of local production of endothelin-1 and of the ET(B)Receptor in the regulation of pulmonary vascular tone

Interaction between locally released endothelin-1 (ET-1) and the endothelial ET(B)receptor could modulate pulmonary vascular tone. We evaluated pulmonary ET-1 clearance and ET-1-ET(B)receptor interaction in the modulation of pulmonary vascular tone. Controls and rats with Monocrotaline (MCT)-induced...

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Bibliographic Details
Published in:Pulmonary pharmacology & therapeutics 2000, Vol.13 (3), p.135-140
Main Authors: Dupuis, J, Jasmin, J F, Prié, S, Cernacek, P
Format: Article
Language:English
Subjects:
Animals
Endothelin-1 - biosynthesis
Endothelin-1 - pharmacology
Lung - metabolism
Male
Oligopeptides - pharmacology
Piperidines - pharmacology
Pulmonary Circulation
Rats
Rats, Sprague-Dawley
Receptor, Endothelin B
Receptors, Endothelin - physiology
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Summary:Interaction between locally released endothelin-1 (ET-1) and the endothelial ET(B)receptor could modulate pulmonary vascular tone. We evaluated pulmonary ET-1 clearance and ET-1-ET(B)receptor interaction in the modulation of pulmonary vascular tone. Controls and rats with Monocrotaline (MCT)-induced pulmonary hypertension (PH) were studied. Lungs were isolated and perfused under constant pressure. The effect of the selective ET(B)antagonist BQ-788 (10(-12)-10(-8)mole) on perfusion flow rate and(125)I-ET-1 extraction was determined. Baseline(125)I-ET-1 extraction was reduced from 62+/-5% in controls to 49+/-10% in PH (P=0.012). BQ-788 inhibited extraction with a higher half-inhibitory dose in the MCT group (-Log ID(50)= 8.9+/-0.4 vs. 9.5+/-0.1, P=0.03). BQ-788 induced a mild reduction in perfusion flow rate of 0.7+/-0.3 ml/min in controls. In the MCT group, this occurred at a lower dose and was more pronounced with a maximal reduction of 3.3+/-0.7 ml/min (P
ISSN:1094-5539
DOI:10.1006/pupt.2000.0242