Analysis of the mechanisms underlying the endothelium-dependent antivasoconstriction of puerarin in rat aorta.

Puerarin, a major isoflavonoid compound from the Chinese herb, Ge-gen (Pueraria lobata), has effective treatment on myocardial and cerebral ischemia, glaucoma and sudden deafness in clinical setting in China. Our present work showed that puerarin (50, 150, 450 microM) concentration-dependently inhibited phenylephrine or KCl-induced contraction only in endothelium-intact rat aortic rings. In Ca(2+)-free solution, the antivasoconstriction of puerarin on phenylephrine was totally deprived. N (G)-nitro-L-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, indomethacin and the three K(+) channel blockers, glibenclamide, tetraethylammonium and Ba(2+) displayed significant inhibitory effects on the antivasoconstriction of puerarin. 8-bromo-cGMP significantly strengthened the action of puerarin. Puerarin (10-160 microM) concentration-dependently induced the NO production in the rat aortic cells. These findings suggested that the antivasoconstriction elicited by puerarin is endothelium-dependent. NO/NO-cGMP pathway, PGI(2) and the opening of K(+) channels sensitive to glibenclamide, tetraethylammonium, and Ba(2+), which might be triggered by the extracellular Ca(2+) influx in the endothelium, appear to contribute to the antivasoconstriction of puerarin.