IngentaConnect INVOLVEMENT OF ENDOTHELIAL CYCLO-OXYGENASE METABOLITES IN NORADRE...

Authors: Wang, Aimin¹; Nishihashi, Tsuyoshi¹; Trandafir, Cristina C¹; Murakami, Shizuka¹; Ji, Xu¹; Shimizu, Yoshiharu²; Kurahashi, Kazuyoshi¹

Source: Clinical and Experimental Pharmacology and Physiology, Volume 32, Number 8, August 2005 , pp. 628-632(5)

Publisher: Blackwell Publishing

Abstract:

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 ofl-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 A₂ (TXA₂) synthetase inhibitor OKY-046 (30 µmol/L) and the TXA₂ 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 ofl-NAME and arachidonic acid is endothelium dependent and is due to endothelial COX metabolites of arachidonic acid.

Keywords: cyclo-oxygenase metabolites; endothelium-dependent contraction; noradrenaline; rat coronary artery

Document Type: Original article

DOI: 10.1111/j.0305-1870.2005.04242.x

Affiliations: 1: Pharmacology Division, RI Center, Kyoto University, Kyoto and 2: Department of Community Health, School of Medicine, Tokai University, Boseidai, Isehara, Kanagawa, Japan

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INVOLVEMENT OF ENDOTHELIAL CYCLO-OXYGENASE METABOLITES IN NORADRENALINE-INDUCED CONTRACTION OF RAT CORONARY ARTERY