Jpn. J. Pharmacol. 85 (1), 47-53 (2001)


Mechanisms Underlying the Induction of Vasorelaxation
in Rat Thoracic Aorta by Sanguinarine

Chien Ming Hu1, Hui Wen Cheng1, Yu Wen Cheng1 and Jaw Jou Kang2,*

1Institute of Pharmaceutical Sciences, Taipei Medical University, Taipei, Taiwan
2Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
*Corresponding author. FAX: +886-2-23410217
E-mail: jjkang@ha.mc.ntu.edu.tw


Abstract: In the present study, the effect of sanguinarine (SANG) on smooth muscle was investigated in thoracic aorta isolated from rats. SANG dose-dependently relaxed the phenylephrine (PE, 3 mM)-precontracted aorta; and the concentrations to produce 50% relaxation were 3.180.37 and 3.421.14 mM, respectively, in intact and denuded aorta. These results suggest that the relaxing effect of SANG was endothelium-independent. The total contraction induced by PE was inhibited in aorta pretreated with SANG at mM concentration. Both phasic and tonic contractions induced by PE were inhibited by SANG independently, which were further supported by the fact that inositol 1,4,5-trisphosphate (IP3) formation and 45Ca2+ influx induced by 3 mM PE in denuded aorta were inhibited by SANG concentration-dependently. In addition, the vasocontraction induced by high-K+ was also inhibited by SANG, however, at higher concentrations. The inhibitory effects of SANG were reversed by dithiothreitol, a thiol reducing agent, implying that the oxidation of critical sulfhydryl groups on key molecules that regulate the smooth muscle contraction were involved. These data suggested that the inhibitory effects of SANG on PE-induced vasocontraction might involve the inhibition of IP3 formation and blockade of calcium channel.

Keywords: Sanguinarine, Aorta, Vasorelaxation, Inositol 1,4,5-trisphosphate, Receptor-operative Ca2+ channel


Copyright The Japanese Pharmacological Society

[Back to TOC]