Mechanisms underlying the induction of vasorelaxation in rat thoracic aorta by sanguinarine

In the present study, the effect of sanguinarine (SANG) on smooth muscle wa s investigated in thoracic aorta isolated from rats. SANG dose-dependently relaxed the phenylephrine (PE, 3 muM)precontracted aorta; and the concentra tions to produce 50% relaxation were 3.18 +/- 0.37 and 3.42 +/- 1.14 muM, r espectively, in intact and denuded aorta. These results suggest that the re laxing effect of SANG was endothelium-independent. The total contraction in duced by PE was inhibited in aorta pretreated with SANG at muM concentratio n. 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 Ca-45(2+) influx induced by 3 muM PE in denuded aorta were inhibited by SANG concentration-dependently. In addition , the vasocontraction induced by high-K+ was also inhibited by SANG, howeve r, at higher concentrations. The inhibitory effects of SANG were reversed b y dithiothreitol, a thiol reducing agent, implying that the oxidation of cr itical sulfhydryl groups on key molecules that regulate the smooth muscle c ontraction were involved. These data suggested that the inhibitory effects of SANG on PE-induced vasocontraction might involve the inhibition of IP3 f ormation and blockade of calcium channel.