School of Sciences of Santa Casa de Misericórdia de Vitoria - EMESCAM, Vitória, ES CEP 29045-402, Brazil.
Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29040-091, Brazil.
Toxicol Appl Pharmacol. 2021 Feb 15;413:115405. doi: 10.1016/j.taap.2021.115405. Epub 2021 Jan 11.
Cardiovascular diseases are among the main causes of mortality in the world. There is evidence of cardiovascular harm after exposure to low lead or mercury concentrations, but the effects of chronic exposure to the association of low doses of these toxic metals are still unknown. This work evaluated after 4 weeks, the association effects of low concentrations of lead and mercury on blood pressure and vascular resistance reactivity. Wistar rats were exposed for 28 days to lead acetate (1st dose of 4 μg/100 g and subsequent doses of 0.05 μg /100 g/day to cover daily losses) and mercury chloride (1st dose of 2.17 μg/kg and subsequent doses of 0.03 μg/kg/ day to cover daily losses) and the control group received saline, i.m. Results showed that treatment increased blood pressure and induced left ventricular hypertrophy. The mesenteric vascular reactivity to phenylephrine and the endothelium-dependent vasodilator response assessed by acetylcholine did not change. Additionally, reduced involvement of vasoconstrictor prostanoids derived from cyclooxygenase was observed in the PbHg group. By other regulatory routes, such as potassium channels, the vessel showed a greater participation of BK channels, and a reduction in the participation of K channels and SK channels. The endothelium-independent smooth muscle relaxation was significantly impaired by reducing cGMP, possibly through the hyperstimulation of Phosphodiesterase-5 (PDE5). Our results suggested that exposure to low doses of lead and mercury triggers this compensatory mechanism, in response to the augment of arterial pressure.
心血管疾病是世界上主要的死亡原因之一。有证据表明，暴露于低浓度的铅或汞会对心血管系统造成损害，但慢性接触低剂量这些有毒金属的联合作用的影响仍不清楚。本工作在 4 周后评估了低浓度铅和汞对血压和血管阻力反应性的联合效应。Wistar 大鼠在 28 天内暴露于醋酸铅（第一剂量为 4μg/100g，随后每天剂量为 0.05μg/100g，以覆盖每日损失）和氯化汞（第一剂量为 2.17μg/kg，随后每天剂量为 0.03μg/kg，以覆盖每日损失），对照组接受生理盐水肌肉注射。结果表明，治疗组血压升高，并诱导左心室肥厚。对苯肾上腺素的肠系膜血管反应性和乙酰胆碱评估的内皮依赖性血管舒张反应性没有变化。此外，在 PbHg 组中观察到源自环氧化酶的血管收缩性前列腺素的参与减少。通过其他调节途径，如钾通道，血管显示出更大的 BK 通道参与，以及 K 通道和 SK 通道参与减少。通过减少 cGMP，内皮非依赖性平滑肌松弛显著受损，可能通过磷酸二酯酶-5（PDE5）的过度刺激。我们的结果表明，暴露于低剂量的铅和汞会触发这种代偿机制，以应对动脉压的升高。
