title: Dihydrogoniothalamin, an Endothelium and NO-Dependent Vasodilator Drug Isolated from Aniba panurensis.
abstract: Dihydrogoniothalamin is a styrylpyrone isolated from the leaves of Aniba panurensis. The present work aimed at investigating the vasorelaxant activity of dihydrogoniothalamin and its underlying mechanism of action in the rat aorta. Dihydrogoniothalamin (0.01-100 µM) induced a concentration-dependent vasodilatation of aortas precontracted with phenylephrine. Endothelium removal or pretreatment of the preparation with NG nitro-L-arginine-methyl-ester abolished the vasodilator response for dihydrogoniothalamin. Pretreatment with calmidazolium did not affect the vasodilator response of dihydrogoniothalamin. On the other hand, wortmannin, a nonselective inhibitor of phosphatidylinositol 3-kinases, and protein kinase B inhibitor IV significantly shifted the concentration-response curve of dihydrogoniothalamin to the right and reduced its maximal effect. A nonselective antagonist of estrogen receptors, ICI 182,780, and a selective antagonist of estrogen receptor α, methyl-piperidino-pyrazole, were able to reduce the relaxation induced by dihydrogoniothalamin, but no effect was observed in the presence of the selective antagonists of estrogen receptor β and G protein-coupled receptor 30, 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), and G-15, respectively. Dihydrogoniothalamin also increased the phosphorylation of the activation sites of endothelial nitric oxide synthase and protein kinase B. The present results led us to conclude that dihydrogoniothalamin is a vasodilator drug acting in an endothelium- and nitric oxide-dependent manner through a mechanism involving the activation of nitric oxide synthase via the phosphatidylinositol 3-kinase/protein kinase B pathway, partially by stimulation of estrogen receptor α.
authors.affiliation: Department of Physiology and Biophysics Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Rezende
authors.affiliation: Department of Physiology and Biophysics Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Grazielle C
authors.initials: GC
authors.lastname: Silva
authors.affiliation: Post-graduate Institute, Medical Sciences College, Belo Horizonte, MG, Brazil.
authors.forename: Rodrigo G
authors.initials: RG
authors.lastname: Corradi
authors.affiliation: Laboratory of Pharmaceutical Sciences, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
authors.forename: Maria Madalena R S
authors.initials: MM
authors.lastname: Teles
authors.affiliation: Laboratory of Pharmaceutical Sciences, Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Barbosa-Filho
authors.affiliation: Department of Physiology and Biophysics Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Lemos
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences. Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Steyner F
authors.initials: SF
authors.lastname: Cortes
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D019770:Lauraceae / Q000737:chemistry*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013343:Styrenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D046509:Tissue Culture Techniques; D014665:Vasodilator Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: C000609608:6-styryl-2-pyrone; D011753:Pyrones; D013343:Styrenes; D014665:Vasodilator Agents; D009569:Nitric Oxide