Nicotine-induced contraction in the rat coronary artery: possible involvement of the endothelium, reactive oxygen species and COX-1 metabolites.

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Kurahashi K, Shirahase H, Nakamura S, Tarumi T, Koshino Y, Wang AM, Nishihashi T, Shimizu Y

Nicotine-induced contraction in the rat coronary artery: possible involvement of the endothelium, reactive oxygen species and COX-1 metabolites.

J Cardiovasc Pharmacol. 2001 Oct;38 Suppl 1:S21-5.

PubMed ID

11811354 [ View in PubMed

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Abstract

Nicotine caused a contraction of the rat coronary artery in the presence of Nomega-nitro-L-arginine methyl ester (L-NAME) and arachidonic acid, and did not in the absence of these agents. The present experiments were undertaken to pharmacologically characterize the nicotine-induced contraction in ring preparations of the rat coronary artery. The contraction was abolished by chemical removal of endothelium saponin. Oxygen radical scavengers, superoxide dismutase and catalase, significantly attenuated the contraction. Cyclooxygenase-1 (COX-1) inhibitors (flurbiprofen, ketoprofen and ketrolack) attenuated the nicotine-induced contraction in a concentration-dependent manner, and cyclooxygenase-2 (COX-2) inhibitors at high concentrations (nimesulide and NS-389) slightly attenuated the contraction. A TXA2 synthetase inhibitor (OKY-046) attenuated the contraction to a small extent only at high concentrations. A TXA2 receptor antagonist (S-1452) attenuated the contraction in a concentration-dependent manner. A nicotinic receptor antagonist (hexamethonium) attenuated the contraction in part and an alpha-adrenoceptor antagonist (prazosin) nearly abolished the contraction. From these results, it was suggested that the contraction induced by nicotine in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium dependent, and involves reactive oxygen species and endothelial COX-1 metabolites of arachidonic acid. Part of the contraction is probably due to release of norepinephrine.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Flurbiprofen	Prostaglandin G/H synthase 1	Protein	Humans	Unknown	Inhibitor	Details
Ketoprofen	Prostaglandin G/H synthase 1	Protein	Humans	Unknown	Inhibitor	Details