Abstract |
Endothelins (ETs) have been implicated in the pathogenesis of hypoxia-induced pulmonary hypertension. We determined whether hypoxic exposure of rats (10% O2-90% N2, 1 atm, 1-48 days) altered contraction to ET in isolated segments of endothelium-denuded extralobar branch pulmonary artery (PA) and aorta. Hypoxic exposure increased hematocrit, right ventricular hypertrophy, and ET-1 plasma concentration. Hypoxia also caused a sustained decrease in PA but not in aorta sensitivity to ET-1. In comparison, hypoxic exposure throughout 12 days decreased time dependently the maximum contraction of PA to ET-1, BaCl2, and KCl. The hypoxia-induced decrease in maximum contraction of PA to ET-1 returned toward normal levels by 21 days and approximated control levels by 48 days. After 14 days of hypoxia, right ventricular hypertrophy correlated with decreased sensitivity of PA to ET-1. After 21 days of hypoxia, PA sensitivity to ET-2 and ET-3 was decreased, and sarafotoxin S6c-induced contraction was abolished. In conclusion, hypoxic exposure time dependently modulates the responsiveness of PA smooth muscle to ETs, BaCl2, and KCl. The hypoxia-induced changes in tissue responsiveness to ET-1 may be associated with increased plasma concentrations of this peptide.
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Authors | R A Bialecki, C S Fisher, W W Murdoch, H G Barthlow, R B Stow, M Mallamaci, W Rumsey |
Journal | The American journal of physiology
(Am J Physiol)
Vol. 274
Issue 4
Pg. L552-9
(04 1998)
ISSN: 0002-9513 [Print] United States |
PMID | 9575873
(Publication Type: Journal Article)
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Chemical References |
- Endothelins
- Vasoconstrictor Agents
- Viper Venoms
- sarafotoxins s6
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Topics |
- Animals
- Endothelins
(pharmacology)
- Hypoxia
(physiopathology)
- Male
- Muscle, Smooth, Vascular
(drug effects, physiopathology)
- Pulmonary Artery
(drug effects, physiopathology)
- Rats
- Rats, Sprague-Dawley
- Time Factors
- Vasoconstriction
(physiology)
- Vasoconstrictor Agents
(pharmacology)
- Viper Venoms
(pharmacology)
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