Vasorelaxant and hypotensive effects of trazodone in Guinea pig

Kim, Shang-Jin; Kang, Hyung-Sub; Kim, Jin-Shang

Korean Journal of Veterinary Research 2005;45(4):485-493.

Shang-Jin Kim, Hyung-Sub Kang, Jin-Shang Kim

Bio-Safety Research Institute, Chonbuk National University

기니픽에서 trazodone의 혈관 이완 및 혈압 하강 효과

김상진, 강형섭, 김진상

전북대학교 생체안전성연구소

Abstract

We studied the effects of trazodone on arterial blood pressure in anesthesized guinea pigs, and on vascular responses in isolated thoracic aorta. Trazodone produced a concentration-dependent relaxation in phenylephrine-precontracted endothelium intact (+E) rings, but not in a KCl-precontracted aortic rings. These relaxant effects of trazodone on +E rings were significantly greater than those on denuded (-E) rings. The trazodone-induced relaxation was suppressed by glibenclamide and tetrabutylammonium, but not by N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), methylene blue (MB), nifedipine, indomethacin, 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC) and clotrimazole. In vivo, infusion of trazodone elicited a significant decrease in arterial blood pressure. Trazodone-induced blood pressure lowering was markedly inhibited by intravenous pretreatment of prazosin but not by pretreatment of saponin, L-NNA, L-NAME, MB, nifedipine, glibenclamide, clotrimazole and NCDC. In addition, trazodone produced an increase in twitch force of isolated papillary muscle and left ventricular pressure of perfused heart. These findings suggest that the endothelium-independent vasorelaxant effect of trazodone may be explained by activation of $Ca^{2+}$-activated and ATP-sensitive $K^+$ channels, and the hypotensive effect of trazodone is not associated with cardiac contraction.

Key Words: aorta, blood pressure, endothelium, hypotension, relaxation, trazodone