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Phosphoramidon blocks big‐endothelin‐1 but not endothelin‐1 enhancement of vascular permeability in the rat
Author(s) -
Lehoux Stéphanie,
Plante Gérard E.,
Sirois Martin G.,
Sirois Pierre,
D'OrléansJuste Pedro
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13397.x
Subject(s) - phosphoramidon , extravasation , evans blue , kidney , vascular permeability , parenchyma , medicine , endothelin 1 , endocrinology , lung , endothelin receptor , chemistry , pathology , receptor
1 Changes in vascular permeability following intravenous injections of human big‐endothelin‐1 (big‐ET‐1) and endothelin‐1 (ET‐1) were measured by extravasation of Evans blue dye (EB, 20 mg kg −1 ) in selected tissues. 2 A low dose of big‐ET‐1 (40 pmol kg −1 ) failed to alter vascular permeability but a dose of 400 pmol kg −1 increased EB extravasation in the trachea, upper and lower bronchi, and lung parenchyma by 55 to 69% ( P < 0.05). Vascular permeability was also enhanced in the liver, spleen, kidney, heart, and diaphragm by 20, 14, 41, 25, and 67%, respectively ( P < 0.05). 3 Upon injection of ET‐1 (400 pmol kg −1 ), EB extravasation increased in the upper and lower bronchi, lung parenchyma, liver, pancreas, kidney, heart, and diaphragm. 4 Administration of ET‐1 and big‐ET‐1 was not associated with significant systemic responses. 5 Pretreatment with phosphoramidon (PA) blocked the response to big‐ET‐1 in all tissues examined but this inhibitor failed to alter the response to ET‐1. 6 We conclude from these results that the dose‐dependent increase in vascular permeability induced by big‐ET‐1 in various tissues follows its conversion to ET‐1 by the endothelin converting enzyme, a PA‐sensitive process.