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INVOLVEMENT OF ENDOTHELIAL CYCLO‐OXYGENASE METABOLITES IN NORADRENALINE‐INDUCED CONTRACTION OF RAT CORONARY ARTERY
Author(s) -
Wang Aimin,
Nishihashi Tsuyoshi,
Trandafir Cristina C,
Murakami Shizuka,
Ji Xu,
Shimizu Yoshiharu,
Kurahashi Kazuyoshi
Publication year - 2005
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.0305-1870.2005.04242.x
Subject(s) - contraction (grammar) , chemistry , medicine , cardiology , artery , vasodilation , pharmacology
SUMMARY 1. Noradrenaline (NA; 0.3 µmol/L) caused a contraction of the rat coronary artery that markedly increased in the presence of the nitric oxide synthase (NOS) inhibitor N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME; 100 µmol/L) and arachidonic acid (1 µmol/L; P < 0.05). 2. The present experiments attempted to elucidate the endothelium dependency of the contraction and to pharmacologically characterize the factors involved in the contraction induced by NA (0.3 µmol/L) in the presence of l ‐NAME and arachidonic acid in ring preparations of the rat coronary artery. 3. The NA (0.3 µmol/L)‐induced contraction was attenuated by a chemical remover of the endothelium (saponin at concentrations of 0.1 and 0.4 mg/mL) in a concentration‐dependent manner ( P < 0.05). 4. The cyclo‐oxygenase (COX)‐1 inhibitor flurbiprofen (0.01–1 µmol/L) and the COX‐2 inhibitor nimesulide (0.01–1 µmol/L) attenuated the NA‐induced contraction in a concentration‐dependent manner and the inhibitory effect of flurbiprofen was significantly more potent than that of nimesulide ( P < 0.05). The 5‐lipoxigenase inhibitor ZM‐230487 (1 µmol/L) did not affect the NA‐induced contraction. 5. The thromboxane A 2 (TXA 2 ) synthetase inhibitor OKY‐046 (30 µmol/L) and the TXA 2 antagonist S‐1452 (0.1–10 µmol/L) did not attenuate the NA‐induced contraction. 6. These results indicate that the contraction induced by NA in the rat coronary artery in the presence of l ‐NAME and arachidonic acid is endothelium dependent and is due to endothelial COX metabolites of arachidonic acid.