Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb.
A possible mechanism of the vasodilator effect of scoparone was investigated. Scoparone (10(-6)-3 x 10(-5) M) dilated rat aortic rings precontracted with phenylephrine in a dose-dependent manner. The presence of endothelium facilitated the vasodilator effect. Scoparone depressed the contractile responses to phenylephrine and serotonin, but not that to potassium chloride. Both the vasoconstriction and O2- production induced by alloxan, a diabetogenic compound, were depressed by scoparone. It appears that scoparone exhibited a free radical scavenger-like effect. The dilatation elicited by acetylcholine was potentiated by scoparone. The dilator activity of scoparone was markedly inhibited by methylene blue and hemoglobin, guanylate cyclase inhibitors. Furthermore, the basal guanosine 3',5'-cyclic monophosphate (cGMP) level was elevated in the presence of scoparone. The dilator activity of scoparone was also inhibited by quinacrine (inhibitor of phospholipase A2) and indomethacin (inhibitor of cyclooxygenase). Our results showed further that the output of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, was enhanced by scoparone. It is suggested that the vasodilator effect of scoparone in rat aorta may be mediated through the enhancement of prostacyclin release, protecting against EDRF inactivation, and activating guanylate cyclase.
Huang
H C
HC
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Lee
C R
CR
Weng
Y I
YI
Lee
M C
MC
Lee
Y T
YT
D000818:Animals; D003374:Coumarins / Q000494:pharmacology*; D006152:Cyclic GMP / Q000032:analysis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D003374:Coumarins; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D011464:Epoprostenol; D006152:Cyclic GMP; C018145:scoparone