Low-level lead exposure changes endothelial modulation in rat resistance pulmonary arteries

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• 作者：Emilia Polaco Covre^a ; David Domingues Freire Jr.^a ; Bruna Miurim Dalfior^b ; Viní ; cius Bermond Marques^a ; Rogé ; rio Faustino Ribeiro Jr.^a ; Maria Tereza Weitzel Dias Carneiro Lima^b ; Leonardo dos Santos^a ; ^{leodossantos@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Heavy metal ; Pulmonary artery ; Vascular reactivity ; Mulvany
• 刊名：Vascular Pharmacology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：85
• 期：Complete
• 页码：21-28
• 全文大小：1053 K

文摘

Lead exposure induces hypertension and endothelial dysfunction. However, the effects on the pulmonary vasculature have not been explored. In this study, rats exposed to lead acetate for seven days (4 μg/100 g on the 1st day and 0.05 μg/100 g/day i.m. subsequently) had lead blood level of 3.9 ± 0.7 μg/dL and increased right ventricular pressures. There was an increased Pb deposition and superoxide anions production in the pulmonary arteries, associated with reduced vasoconstriction but unchanged endothelium-dependent vasodilatation to acetylcholine (ACh). In both groups, inhibition of the nitric oxide (NO) synthase with L-NAME blocked the response to ACh, while indomethacin (cycloxygenase inhibitor) had no effect. Incubation with nonspecific potassium channel blocker (tetraethylammonium) reduced the ACh-induced vasodilatation only in the Pb group. Apamin (SK_Ca channel blocker) and 4-aminopyridine (K_v channel blocker), but not iberiotoxin (BK_Ca channel blocker), also inhibited this response in the Pb group. The vasodilatation to exogenous NO was reduced by Pb, while relaxation to the cGMP analogue was similar between groups. Concordantly, the protein level of soluble guanylate cyclase (sGC) was reduced. In conclusion, short-term and low-level exposure to Pb changes pulmonary haemodynamic and increases oxidative stress. The pulmonary vasculature exhibited increased hyperpolarization by the K_v and SK_Ca channels, probably as a compensatory mechanism to the decreased responsiveness to NO.