Effects of endothelin-1 and conversion of big endothelin-1 in the isolated perfused rabbit lung.
J Appl Physiol (1985)
; 72(6): 2387-92, 1992 Jun.
Article
in En
| MEDLINE
| ID: mdl-1629095
ABSTRACT
We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Precursors
/
Endothelins
/
Lung
Limits:
Animals
Language:
En
Journal:
J Appl Physiol (1985)
Journal subject:
FISIOLOGIA
Year:
1992
Type:
Article
Affiliation country:
Japan