title: Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas.
abstract: Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin-renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4mg/100g, subsequent doses 0.05mg/100g, im) or vehicle for 30 days. Treatment increased lead blood levels (12μg/dl), blood pressure, and aortic ring contractile response to phenylephrine (1nM-100mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on Rmax decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A2/prostaglandin H2 receptor antagonist SQ 29,548, TXA2 synthase inhibitor furegrelate, EP1 receptor antagonist SC 19220, and ACE inhibitor and AT1 receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O2(-) liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT1 receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb(2+) (12µg/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin-angiotensin system activity.
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil. Electronic address: ednasilveira17@gmail.com.
authors.forename: Edna Aparecida
authors.initials: EA
authors.lastname: Silveira
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Fabiana Dayse Magalhães
authors.initials: FD
authors.lastname: Siman
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Thaís
authors.initials: T
authors.lastname: de Oliveira Faria
authors.affiliation: Center for Exact Sciences, Chemistry Department, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Marcos Vinícius Altoé
authors.initials: MV
authors.lastname: Vescovi
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Lorena Barros
authors.initials: LB
authors.lastname: Furieri
authors.affiliation: Department of Morphology, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Juliana Hott Fúcio
authors.initials: JH
authors.lastname: Lizardo
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Alessandra Simão
authors.initials: AS
authors.lastname: Padilha
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
authors.forename: Dalton Valentim
authors.initials: DV
authors.lastname: Vassallo
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects*; D002908:Chronic Disease; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007855:Lead Poisoning / Q000378:metabolism / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; C056165:acetovanillone; D013482:Superoxide Dismutase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: Free radicals; Hypertension; Lead acetate; Local renin–angiotensin system; NO; ROS; Rat aorta; Vasoconstrictor prostanoids