In vitro pharmacological actions of sinomenine on the smooth muscle and the endothelial cell activity in rat aorta

Vasodilating actions of sinomenine were examined using rat aorta ring strips. Sinomenine (0.1 to 100 μM) dilated norepinephrine (NE, 5 μM)-induced vasoconstriction in a concentration-dependent manner reaching 68.8 ± 5.1% (n = 6, P < 0.01) at a concentration of 100 μM. Sinomenine (100 μM) also attenuated KCl (60 mM) and phorbol 12, 13-dibutyrate (PDB, a protein kinase C, PK-C, activator, 300 nM)-induced vasoconstriction by 86.9 ± 8.5% (n = 6, P < 0.01) and 49.9 ± 9.8% (n = 6, P < 0.01), respectively. Pretreatment with nicardipine (a Ca2+ channel antagonist), staurosporine (a PK-C inhibitor), NG-monomethyl-l-arginine acetate (l-NMMA, a nitric oxide, NO, synthesis inhibitor), and indomethacin (a cyclooxygenase inhibitor) were carried out. Nicardipine (0.1 μM) led to a significant decrease in the vasodilating potential of sinomenine (at 100 μM, 68.8 ± 5.1% vs. 35.5 ± 6.9%; n = 5, P < 0.001). Pretreatment with staurosporine (30 nM) reduced sinomenine-associated vasodilation from 68.8 ± 5.1% to 49.5 ± 7.7% (n = 5, P < 0.001), and l-NMMA (100 μM) and indomethacin (10 μM), to 25.3 ± 2.3% (n = 5, P < 0.001) and to 37.1 ± 9.3% (n = 5, P < 0.001), respectively. The responses were almost similar to the results without endothelium. Therefore, these results indicate that sinomenine causes the vasorelaxation by the mechanisms involved with the inhibitions of Ca2+ channel and PK-C activity, and also with the activations of NO and prostaglandin (PG) I2 syntheses in endothelium.