title: Endothelial nitric oxide production stimulated by the bioflavonoid chrysin in rat isolated aorta.
abstract: In the present study, the effects of the bioflavonoid chrysin (5,7-dihydroxyflavone) were analysed on nitric oxide (NO) production from vascular endothelium. In aortic rings, incubation with chrysin or acetylcholine (both at 10 microM) increased L-NAME-sensitive endothelial NO release as measured using the fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2 DA). Moreover, chrysin increased cGMP accumulation only in aortic rings with endothelium. However, at this concentration, chrysin had no effect either on basal or on NADPH-stimulated vascular superoxide production. Moreover, at this low concentration, chrysin, similar to acetylcholine, induced aortic relaxation, which was abolished by both endothelial deprivation and NO synthase inhibition. Endothelium-dependent relaxation induced by chrysin was unaltered by removal of extracellular calcium and incubation with the intracellular calcium chelator BAPTA, while the phosphatidylinositol (PI)-3 kinase inhibitor wortmannin suppressed the endothelial dependence. In conclusion, chrysin stimulated NO release from endothelial cells leading to vascular cGMP accumulation and subsequent endothelium dependent aortic relaxation. Chrysin-stimulated NO release is calcium independent and possibly mediated via PI3-kinase.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
authors.forename: Inmaculada Concepción
authors.initials: IC
authors.lastname: Villar
authors.forename: Rocío
authors.initials: R
authors.lastname: Vera
authors.forename: Milagros
authors.initials: M
authors.lastname: Galisteo
authors.forename: Francisco
authors.initials: F
authors.lastname: O'Valle
authors.forename: Miguel
authors.initials: M
authors.lastname: Romero
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: Juan
authors.initials: J
authors.lastname: Duarte
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D014665:Vasodilator Agents; D009569:Nitric Oxide; C043561:chrysin