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KMID : 0359320030430040587
Korean Journal of Veterinary Research
2003 Volume.43 No. 4 p.587 ~ p.595
Mechanism of the relaxant action of Trazodone in isolated rat aorta



Abstract
The aim of this study was to investigate trazodone¢¥s effect on vasorelaxation and blood pressure lowering and to examine its underlying mechanism of action in isolated thoracic aorta and anesthesized rats. Precontracted aortic rings with high KCI were relaxed with trazodone, at concentrations of 50 ¥ìM or greater. However, precontracted rings with phenylophrine (PE) were relaxed with trazodone, at concentrations of 0.03 ¥ìM or greater, in concentration-dependent manner. These relaxant effects of trazodone on endothelium intact rat aortic rings were significantly greater than those on denuded rings. The trazodone-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA) and N(omega)-nitro-L-arginine methyl ester (L-NAME), guanylate cyclase inhibitors, methylene blue and 1H-¡²1,2,4¡³oxadiazolo¡²4,3-a¡³quinoxalin-1-one (ODQ), a Ca^(2+)-activated K^(+) channel blocker, tetrabutylammonium (TBA), a Ca^(2+) channel blocker, nifedipine, Na^(+) channel blockers, lidocaine and procaine, and removal of extracellular Na^(+), but not by aminoguanidine, 2-nitro-4-carboxyphenyl-n, n-diphenylcarbamate (NCDC), indomethacin, glibenclamide and clotrimazole. In vivo, infusion of trazodone elicited significant decrease in arterial blood pressure. Trazodone-induced decrease in blood pressure was markedly inhibited by pretreatment of intravenous injection of saponin, L-NNA, methylene blue, TBA, lidocaine or nifedipine. These findings suggest that the endothelium-dependent relaxation and decrease in blood pressure induced by trazodone is mediated by release of NO from the endothelium, activation of TBA-sensitive Ca^(2+)-activated K^(+) channels or inhibition of Ca^(2+) entry through voltage-gated channel.
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