Ra. Bialecki et al., HYPOXIC EXPOSURE TIME DEPENDENTLY MODULATES ENDOTHELIN-INDUCED CONTRACTION OF PULMONARY-ARTERY SMOOTH-MUSCLE, American journal of physiology. Lung cellular and molecular physiology, 18(4), 1998, pp. 552-559
Endothelins (ETs) have been implicated in the pathogenesis of hypoxia-
induced pulmonary hypertension. We determined whether hypoxic exposure
of rats (10% O-2-90% N-2, 1 atm, 1-48 days) altered contraction to ET
in isolated segments of endothelium-denuded extralobar branch pulmona
ry 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 de
pendently the maximum contraction of PA to ET-1, BaCl2, and KCl. The h
ypoxia-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 correlat
ed 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-in
duced contraction was abolished. In conclusion, hypoxic exposure time
dependently modulates the responsiveness of PA smooth muscle to ETs, B
aCl2, and KCl. The hypoxia-induced changes in tissue responsiveness to
ET-1 may be associated with increased plasma concentrations of this p
eptide.