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Increased response to big endothelin‐1 in atherosclerotic human coronary artery: functional evidence for up‐regulation of endothelin‐converting enzyme activity in disease
Author(s) -
Maguire Janet J,
Davenport Anthony P
Publication year - 1998
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 - 10.1038/sj.bjp.0702102
Subject(s) - coronary arteries , coronary artery disease , endothelin 1 , medicine , endothelin receptor , cardiology , artery , endothelium , pathogenesis , endocrinology , receptor
Overproduction of the potent vasoconstrictor peptide endothelin‐1 (ET‐1) is implicated in the pathogenesis of coronary artery disease. In endothelium‐denuded human coronary arteries the response to big ET‐1 was significantly enhanced in atherosclerotic arteries (coronary artery disease, CAD; n =7) with an EC 50 value of 96 n M (57–161 n M , 95% C.I.) compared to 274 n M (205–365 n M ) in non‐diseased arteries (dilated cardiomyopathy, DCM; n =10) (Mann‐Whitney U ‐test, P <0.05 ). Higher levels of immunoreactive endothelin (ET) could be detected by radioimmunoassay in bathing medium taken from CAD arteries than from DCM arteries (2.8±0.5 n M , n =5 vs 1.1±0.2 n M , n =7) (Student's two‐tailed t ‐test, P <0.05 ). There were no differences in responses of arteries from either group to ET‐1 (EC 50 10 n M , CAD vs 14 n M , DCM). The enhanced response of atherosclerotic human coronary arteries to big ET‐1 appears to be due to up‐regulation of endothelin‐converting enzyme (ECE) activity rather than to an augmented response of the arteries to ET‐1. This non‐endothelial ECE may therefore be an important therapeutic target in coronary artery disease. British Journal of Pharmacology (1998) 125 , 238–240; doi: 10.1038/sj.bjp.0702102