Activation of K⁺ channels and Na⁺/K⁺ ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats

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• 作者：Jonaina Fiorim^a ; ^{nanafiorim@hotmail.com} ; Rogé ; rio Faustino Ribeiro Jú ; nior^a ; ^{faustino43@oi.com.br} ; Bruna Fernades Azevedo^a ; ^{brunafernandes.azevedo@gmail.com} ; Maylla Ronacher Simõ ; es^a ; ^{yllars@hotmail.com} ; Alessandra Simã ; o Padilha^a ; ^{ale_spadilha@yahoo.com.br} ; Ivanita Stefanon^a ; ^{ivanita@pq.cnpq.br} ; Maria Jesus Alonso^c ; ^{mariajesus.alonso@urjc.es} ; Mercedes Salaices^b ; ^{mercedes.salaices@uam.es} ; Dalton Valentim Vassallo^a ; ^{daltonv2@terra.com.br}
• 关键词：Lead ; Nitric oxide ; Na+/K+-ATPase activity ; Potassium channels
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2012
• 期刊代码：58_0041008x
• 类别：pha
• 出版时间：1 July, 2012
• 卷：262
• 期：1
• 页码：22-31
• 文件大小：867 K

摘要

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 渭g/100 g, subsequent doses 0.05 渭g/100 g, 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^{鈭?/sup> production, and apocynin (0.3 渭M), 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 渭M) plus L-NAME (100 渭M), aminoguanidine (50 渭M) 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 渭M) or charybdotoxin (0.1 渭M), 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.}