Wiggers Giulia Alessandra, Stefanon Ivanita, Padilha Alessandra Simão, Peçanha Franck Maciel, Vassallo Dalton Valentim, Oliveira Edilamar Menezes
Department of Physiological Sciences, Federal University of Espírito Santo, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2008 Mar;147(2):252-60. doi: 10.1016/j.cbpc.2007.10.003. Epub 2007 Nov 12.
Exposure to mercury at nanomolar level affects cardiac function but its effects on vascular reactivity have yet to be investigated. Pressor responses to phenylephrine (PHE) were investigated in perfused rat tail arteries before and after treatment with 6 nM HgCl2 during 1 h, in the presence (E+) and absence (E-) of endothelium, after L-NAME (10(-4) M), indomethacin (10(-5 )M), enalaprilate (1 microM), tempol (1 microM) and deferoxamine (300 microM) treatments. HgCl2 increased sensitivity (pD2) without modifying the maximum response (Emax) to PHE, but the pD2 increase was abolished after endothelial damage. L-NAME treatment increased pD2 and Emax. However, in the presence of HgCl2, this increase was smaller, and it did not modify Emax. After indomethacin treatment, the increase of pD2 induced by HgCl2 was maintained. Enalaprilate, tempol and deferoxamine reversed the increase of pD2 evoked by HgCl2. HgCl2 increased the angiotensin converting enzyme (ACE) activity explaining the result obtained with enalaprilate. Results suggest that at nanomolar concentrations HgCl2 increase the vascular reactivity to PHE. This response is endothelium mediated and involves the reduction of NO bioavailability and the action of reactive oxygen species. The local ACE participates in mercury actions and depends on the angiotensin II generation.
纳摩尔水平的汞暴露会影响心脏功能,但其对血管反应性的影响尚待研究。在用6 nM HgCl₂处理1小时前后,在有内皮(E+)和无内皮(E-)的情况下,以及在L-NAME(10⁻⁴ M)、吲哚美辛(10⁻⁵ M)、依那普利拉(1 μM)、Tempol(1 μM)和去铁胺(300 μM)处理后,研究了灌注大鼠尾动脉对去氧肾上腺素(PHE)的升压反应。HgCl₂增加了对PHE的敏感性(pD₂),而不改变最大反应(Emax),但在内皮损伤后pD₂的增加被消除。L-NAME处理增加了pD₂和Emax。然而,在存在HgCl₂的情况下,这种增加较小,并且没有改变Emax。吲哚美辛处理后,HgCl₂诱导的pD₂增加得以维持。依那普利拉、Tempol和去铁胺逆转了HgCl₂引起的pD₂增加。HgCl₂增加了血管紧张素转换酶(ACE)活性,这解释了依那普利拉的实验结果。结果表明,在纳摩尔浓度下,HgCl₂增加了血管对PHE的反应性。这种反应是由内皮介导的,涉及一氧化氮生物利用度的降低和活性氧的作用。局部ACE参与汞的作用,并依赖于血管紧张素II的生成。