Nicotine-induced contraction in the rat coronary artery: possible involvement of the endothelium, reactive oxygen species and COX-1 metabolites.
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.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N CHEMICAL GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
arachidonic acid norepinephrine nicotine saponin Oxygen flurbiprofen ketoprofen ketrolack nicotine nimesulide Nicotine NS-389 Nomega-nitro-L-arginine methyl ester TXA2 OKY-046 TXA2 S-1452 Nicotine oxygen nicotinic receptor alpha-adrenoceptor hexamethonium COX-1 superoxide dismutase catalase Cyclooxygenase-1 COX-1 cyclooxygenase-2 COX-2 TXA2 synthetase TXA2 receptor COX-1 prazosin L-NAME nicotine arachidonic acid L-NAME arachidonic acid oxygen