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 microM) dilated norepinephrine (NE, 5 microM)-induced vasoconstriction in a concentration-dependent manner reaching 68.8+/-5.1% (n=6, P<0.01) at a concentration of 100 microM. Sinomenine (100 microM) 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 microM) led to a significant decrease in the vasodilating potential of sinomenine (at 100 microM, 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 microM) and indomethacin (10 microM), 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.
Nishida
Seiichiro
S
Department of Pharmacology, Division of Crude and Herbal Medicine, Nara Medical University, School of Medicine, Kashihara, Nara 634-8521, Japan.
Satoh
Hiroyasu
H
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology* / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents
D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009019:Morphinans; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C009271:sinomenine; D052250:Nitric Oxide Synthase Type III; D011493:Protein Kinase C