title: Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.
abstract: Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil. Electronic address: rogeriofaustinoribeiro@hotmail.com.
authors.forename: Rogério Faustino
authors.initials: RF
authors.lastname: Ribeiro Júnior
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Vinicius Bermond
authors.initials: VB
authors.lastname: Marques
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Dieli Oliveira
authors.initials: DO
authors.lastname: Nunes
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Karoline de Sousa
authors.initials: Kde S
authors.lastname: Ronconi
authors.affiliation: Department of Morphology, Federal University of Espírito Santo, Brazil.
authors.forename: Julia F P
authors.initials: JF
authors.lastname: de Araújo
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Paula Lopes
authors.initials: PL
authors.lastname: Rodrigues
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Alessandra Simão
authors.initials: AS
authors.lastname: Padilha
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Dalton Valentim
authors.initials: DV
authors.lastname: Vassallo
authors.affiliation: Department of Morphology, Federal University of Espírito Santo, Brazil.
authors.forename: Jones B
authors.initials: JB
authors.lastname: Graceli
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004967:Estrogens / Q000097:blood; D005260:Female; D006439:Hemodynamics; D008638:Mesenteric Arteries / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D063177:Pulse Wave Analysis; D051381:Rats; D017208:Rats, Wistar; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D066253:Vascular Remodeling / Q000187:drug effects; D059289:Vascular Stiffness / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004967:Estrogens; D014220:Trialkyltin Compounds; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; C011559:tributyltin; D003094:Collagen; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester
keywords: Arterial remodelling; Endothelial dysfunction; Oxidative stress; Resistance artery; Tributyltin chloride