Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, 29040-091, Brazil.
Health Science Center of Vitória-EMESCAM, Vitória, ES, 29045-402, Brazil.
Cardiovasc Toxicol. 2018 Apr;18(2):161-174. doi: 10.1007/s12012-017-9427-x.
Heavy metal exposure is associated with cardiovascular diseases such as myocardial infarction (MI). Vascular dysfunction is related to both the causes and the consequences of MI. We investigated whether chronic exposure to low doses of mercury chloride (HgCl) worsens MI-induced endothelial dysfunction 7 days after MI. Male Wistar rats were divided into four groups: Control (vehicle), HgCl (4 weeks of exposure), surgically induced MI and combined HgCl-MI. Morphological and hemodynamic measurements were used to characterize the MI model 7 days after the insult. Vascular reactivity was evaluated in aortic rings. Chronic HgCl exposure did not cause more heart injury than MI alone in terms of the morphological or hemodynamic parameters. Vascular reactivity increased in all groups, but the combination of HgCl-MI increased the vasorelaxation induced by ACh compared with the HgCl and MI groups. Results showed reduced endothelial nitric oxide synthase (eNOS) protein expression in the MI group; increased iNOS activity in the HgCl-MI group, although without enough magnitude to reverse the reduction in NO bioavailability; and increased phenylephrine response in the HgCl-MI group due to an increase in ROS production, notably via xanthine oxidase (XO). Results suggest that the combination of 1 month pre-exposure of HgCl before MI changed the endothelial generation of oxidative stress induced by mercury exposure from NADPH oxidase pathway to XO (xanthine oxidase)-dependent ROS production.
重金属暴露与心肌梗死（MI）等心血管疾病有关。血管功能障碍与 MI 的原因和后果都有关。我们研究了慢性低剂量氯化汞（HgCl）暴露是否会加重 MI 后 7 天的内皮功能障碍。雄性 Wistar 大鼠分为四组：对照组（载体）、HgCl（暴露 4 周）、手术诱导的 MI 和联合 HgCl-MI。形态学和血液动力学测量用于在损伤后 7 天表征 MI 模型。在主动脉环中评估血管反应性。慢性 HgCl 暴露在形态或血液动力学参数方面并未比单独 MI 造成更多的心脏损伤。所有组的血管反应性均增加，但与 HgCl 和 MI 组相比，HgCl-MI 联合增加了 ACh 诱导的血管舒张。结果表明，MI 组内皮型一氧化氮合酶（eNOS）蛋白表达减少；HgCl-MI 组中 iNOS 活性增加，但不足以逆转 NO 生物利用度的降低；HgCl-MI 组中苯肾上腺素反应增加，这是由于 ROS 产生增加，特别是通过黄嘌呤氧化酶（XO）。结果表明，HgCl 暴露前 1 个月的预暴露与 MI 的组合改变了由 NADPH 氧化酶途径引起的汞暴露引起的内皮氧化应激的产生，从 NADPH 氧化酶途径转向 XO（黄嘌呤氧化酶）依赖性 ROS 产生。
