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Modulation of endothelium‐dependent contractions by chronic inhibition of nitric oxide synthase in the rat aorta
Author(s) -
Qu Chen,
Leung Susan W.S.,
Vanhoutte Paul M.,
Man Ricky Y.K.
Publication year - 2008
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.22.1_supplement.1128.7
Subject(s) - nitric oxide synthase , endothelium , nitric oxide , enos , medicine , endocrinology , chemistry , nitroarginine , endothelial nos , cyclooxygenase , acetylcholine , antagonist , thromboxane , receptor , enzyme , biochemistry , platelet
Acute inhibition of nitric oxide (NO) synthase (NOS) augments the release of endothelium‐derived contracting factor (EDCF). The present study investigates whether or not chronic inhibition of NOS modulates endothelium‐dependent contractions (EDC). Eighteen weeks old male Sprague Dawley rats were treated for 6 weeks with vehicle or the NOS inhibitor, N‐nitro‐L‐arginine methyl ester (L‐NAME). Aortic rings with or without endothelium were used for isometric tension recording. Chronic NOS inhibition increased systolic blood pressure and reduced acetylcholine‐induced relaxations in rings with endothelium. This reduction was reversed by L‐arginine (1 mM). In quiescent aortic rings, A23187 caused contractions, which were greater in the presence of the endothelium and after L‐NAME treatment. These contractions were abolished by the cyclooxygenase (COX)‐2 (NS‐398) but not the COX‐1 (SC‐560) inhibitor, and by the selective thromboxane (TP)‐receptor antagonist (terutroban). In the treated group, COX‐1 and COX‐2 expressions, as determined by Western blotting, were up‐regulated while the TP receptor expression remained unchanged, and eNOS expression and NO level became lower. These experiments demonstrate that chronic NOS inhibition in the rat enhances EDC by inducing COX‐2 expression and augmenting the production of EDCF. (Supported by the Research Grant Council of Hong Kong)