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Reduction of contractions to phenylephrine by L‐NAME in the carotid artery of mice with endothelial overexpression of endothelin‐1
Author(s) -
Baretella Oliver,
Li François YL,
Chung Sookja K,
Vanhoutte Paul M
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1129.5
Subject(s) - phenylephrine , agonist , endocrinology , vasodilation , medicine , endothelin 1 , vasoconstriction , endothelium , acetylcholine , endothelin receptor , chemistry , vascular smooth muscle , receptor , smooth muscle , blood pressure
The release of endothelium‐derived contracting factors (EDCF) is increased by exogenous endothelin‐1 (ET‐1). Experiments were designed to determine whether or not endothelial overexpression of ET‐1 affects vascular responsiveness. Carotid artery rings with endothelium of control mice and mice with endothelial overexpression of ET‐1 (TET‐1) were contracted with the α1‐adrenoceptor agonist phenylephrine in the absence or presence of the eNOS inhibitor L‐NAME and exposed to acetylcholine. After washout, the rings were contracted with increasing concentrations of the TP receptor agonist U46619. EDCF‐mediated increases in tension caused by acetylcholine were augmented in TET‐1 arteries compared to controls both in the absence and presence of LNAME. In the presence of the latter, TET‐1 rings showed stronger contractions to U46619 than controls. By contrast, contractions to phenylephrine were reduced by L‐NAME in TET‐1 arteries with a rightward shift and loss of the sigmoidal shape of the concentration‐response curve. These results imply a role of endothelial ET‐1 in EDCF‐mediated contractions and indicate an increased TXA2 receptor signaling in vascular smooth muscle cells. They do not provide an explanation for the decreased response to α1‐adrenergic activation in TET‐1 arteries in the absence of NO. Sponsored by the Swiss National Science Foundation and the Hong Kong Research Grant Council.