VASODILATOR EFFECTS OF VISNAGIN IN ISOLATED RAT VASCULAR SMOOTH-MUSCLE

Visnagin (4-methoxy-7-methyl-5H-furo [3,2-g][1]-benzopyran-5-one) is a n active principle of the fruit of Ammi visnaga, a plant traditionally used in cardiovascular disorders. We have studied its vasodilator eff ects in rat vascular smooth muscle. The results demonstrated that visn agin inhibited the contractile responses induced in rat aortic rings b y: (a) KCl or increases of extracellular Ca2+ in KCl depolarized aorti c rings, its effects being more potent against low (20 mM) than high ( 80 mM) KCl-induced contractions, (b) noradrenaline in Ca2+-containing solution and less effectively those in Ca2+-free solution and (c) phor bol 12-myristate 13-acetate (PMA) in a Ca2+-containing and with a lowe r potency in Ca2+-free medium. The relaxation induced by visnagin in a orta precontracted with noradrenaline was not affected by endothelium removal. Additionally, visnagin inhibited the spontaneous myogenic con tractions of portal veins. The results showed that visnagin inhibited vascular smooth muscle contractility by acting at multiple sites. In t he range of 10(-6) M to 5 X 10(-5) M visnagin appears to inhibit only the contractions mediated by Ca2+ entry through pathways with low sens itivity to classical Ca2+-entry blockers, i.e. agonist-, PMA-or mild d epolarization-induced Ca2+ entry. Therefore, the vasodilator profile o f visnagin, is not that of typical Ca2+-entry blockers which preferent ially inhibit the contractions induced by strong depolarizations.:At h igher concentrations (>5 x 10(-5) M) visnagin causes non-specific inhi bition of vascular smooth muscle contractility.