title: The vasorelaxant effect of gallic acid involves endothelium-dependent and -independent mechanisms.
abstract: The mechanisms of action involved in the vasorelaxant effect of gallic acid (GA) were examined in the isolated rat thoracic aorta. GA exerted a relaxant effect in the highest concentrations (0.4-10mM) in both endothelium-intact and endothelium-denuded aortic rings. Pre-incubation with L-NAME, ODQ, calmidazolium, TEA, 4-aminopyridine, and barium chloride significantly reduced the pEC50 values. Moreover, this effect was not modified by indomethacin, wortmannin, PP2, glibenclamide, or paxillin. Pre-incubation of GA (1, 3, and 10mM) in a Ca(2+)-free Krebs solution attenuated CaCl2-induced contractions and blocked BAY K8644-induced vascular contractions, but it did not inhibit a contraction induced by the release of Ca(2+) from the sarcoplasmatic reticulum stores. In addition, a Western blot analysis showed that GA induces phosphorylation of eNOS in rat thoracic aorta. These results suggest that GA induces relaxation in rat aortic rings through an endothelium-dependent pathway, resulting in eNOS phosphorylation and opening potassium channels. Additionally, the relaxant effect by an endothelium-independent pathway involves the blockade of the Ca(2+) influx via L-type Ca(2+) channels.
authors.affiliation: Department of Pharmacology, Laboratory of Molecular and Biochemistry Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Lais Moraes
authors.initials: LM
authors.lastname: de Oliveira
authors.affiliation: Department of Pharmacology, Laboratory of Molecular and Biochemistry Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Thiago Sardinha
authors.initials: TS
authors.lastname: de Oliveira
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Rafael Menezes
authors.initials: RM
authors.lastname: da Costa
authors.affiliation: Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Eric
authors.initials: E
authors.lastname: de Souza Gil
authors.affiliation: Department of Pharmacology, Laboratory of Pharmacology of Natural Products, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
authors.forename: Elson Alves
authors.initials: EA
authors.lastname: Costa
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Rita de Cassia Aleixo Tostes
authors.initials: Rde C
authors.lastname: Passaglia
authors.affiliation: Institute of Health Sciences, Federal University of Goias, Jatai, GO, Brazil.
authors.forename: Fernando Paranaíba
authors.initials: FP
authors.lastname: Filgueira
authors.affiliation: Department of Pharmacology, Laboratory of Molecular and Biochemistry Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil. Electronic address: pcghedini@gmail.com.
authors.forename: Paulo César
authors.initials: PC
authors.lastname: Ghedini
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005707:Gallic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D014665:Vasodilator Agents; D005707:Gallic Acid; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
keywords: Calcium channel; Gallic acid; Nitric oxide; Potassium channels; Rat thoracic aorta; Vasorelaxant