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 an active principle of the fruit of Ammi visnaga, a plant traditionally used in cardiovascular disorders. We have studied its vasodilator effects in rat vascular smooth muscle. The results demonstrated that visnagin inhibited the contractile responses induced in rat aortic rings by: (a) KCl or increases of extracellullar Ca2+ in KCl depolarized aortic rings, its effects being more potent against low (20 mM) than high (80 mM) KCl-induced contractions, (b) noradrenaline in Ca(2+)-containing solution and less effectively those in Ca(2+)-free solution and (c) phorbol 12-myristate 13-acetate (PMA) in a Ca(2+)-containing and with a lower potency in Ca(2+)-free medium. The relaxation induced by visnagin in aorta precontracted with noradrenaline was not affected by endothelium removal. Additionally, visnagin inhibited the spontaneous myogenic contractions of portal veins. The results showed that visnagin inhibited vascular smooth muscle contractility by acting at multiple sites. In the 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 sensitivity to classical Ca(2+)-entry blockers, i.e. agonist-, PMA- or mild depolarization-induced Ca2+ entry. Therefore, the vasodilator profile of visnagin, is not that of typical Ca(2+)-entry blockers which preferentially inhibit the contractions induced by strong depolarizations. At higher concentrations (> 5 x 10(-5) M) visnagin causes non-specific inhibition of vascular smooth muscle contractility.
Duarte
J
J
Department of Pharmacology, School of Pharmacy, University of Granada, Spain.
Pérez-Vizcaíno
F
F
Torres
A I
AI
Zarzuelo
A
A
Jiménez
J
J
Tamargo
J
J
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007666:Khellin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D007666:Khellin; D013755:Tetradecanoylphorbol Acetate; C044999:visnagin; D002118:Calcium; D009638:Norepinephrine