title: Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas.
abstract: Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 µg/100 g, subsequent dose 0.05 µg/100 g, i.m. to cover daily loss) or vehicle; blood levels attained at the end of treatment were 9.98 µg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM-100 µM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 µM) or sodium nitroprusside (0.01 nM-0.3 µM). Endothelium removal, N(G)-nitro-L-arginine methyl ester (100 µM) and tetraethylammonium (2 mM) increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 µM) increased but losartan (10 µM) and enalapril (10 µM) reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na(+)/K(+)-ATPase functional activity, plasma angiotensin-converting enzyme (ACE) activity, protein expression of the Na(+)/K(+)-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS), and inducible nitric oxide synthase (iNOS). Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+)/K(+)-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, Espírito Santo, Brazil.
authors.forename: Jonaina
authors.initials: J
authors.lastname: Fiorim
authors.forename: Eduardo Hertel
authors.initials: EH
authors.lastname: Ribeiro
authors.forename: Edna A
authors.initials: EA
authors.lastname: Silveira
authors.forename: Alessandra S
authors.initials: AS
authors.lastname: Padilha
authors.forename: Marcos Vinícius A
authors.initials: MV
authors.lastname: Vescovi
authors.forename: Honério C
authors.initials: HC
authors.lastname: de Jesus
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.forename: Dalton V
authors.initials: DV
authors.lastname: Vassallo
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D045462:Endothelium-Dependent Relaxing Factors / Q000097:blood*; D007854:Lead / Q000633:toxicity*; D007855:Lead Poisoning / Q000097:blood* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D007854:Lead; D000254:Sodium-Potassium-Exchanging ATPase