title: Activation of K+ channels and Na+/K+ ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats.
abstract: Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K+ channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K+ channels and Na+/K+)-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent doses 0.05 μg/100g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilator response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O₂⁻ production, and apocynin (0.3 μM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K+-induced relaxation curves. Ouabain (100 μM) plus L-NAME (100 μM), aminoguanidine (50 μM) or tetraethylammonium (TEA, 2 mM) reduced the K+-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 μM) or charybdotoxin (0.1 μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K+ channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil. nanafiorim@hotmail.com
authors.forename: Jonaina
authors.initials: J
authors.lastname: Fiorim
authors.forename: Rogério Faustino
authors.initials: RF
authors.lastname: Ribeiro
authors.forename: Bruna Fernades
authors.initials: BF
authors.lastname: Azevedo
authors.forename: Maylla Ronacher
authors.initials: MR
authors.lastname: Simões
authors.forename: Alessandra Simão
authors.initials: AS
authors.lastname: Padilha
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Alonso
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.forename: Dalton Valentim
authors.initials: DV
authors.lastname: Vassallo
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009942:Organometallic Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D009942:Organometallic Compounds; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; C008261:lead acetate; D010100:Oxygen