Physiological Sciences Post-Graduation Program, Federal University of Espírito Santo, Vitoria, Espírito Santo, Brazil.
PLoS One. 2011 Apr 11;6(4):e18730. doi: 10.1371/journal.pone.0018730.
Chronic lead exposure causes hypertension and cardiovascular disease. Our purpose was to evaluate the effects of acute exposure to lead on arterial pressure and elucidate the early mechanisms involved in the development of lead-induced hypertension.
METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats were treated with lead acetate (i.v. bolus dose of 320 µg/Kg), and systolic arterial pressure, diastolic arterial pressure and heart rate were measured during 120 min. An increase in arterial pressure was found, and potential roles of the renin-angiotensin system, Na(+),K(+)-ATPase and the autonomic reflexes in this change in the increase of arterial pressure found were evaluated. In anesthetized rats, lead exposure: 1) produced blood lead levels of 37±1.7 µg/dL, which is below the reference blood concentration (60 µg/dL); 2) increased systolic arterial pressure (Ct: 109±3 mmHg vs Pb: 120±4 mmHg); 3) increased ACE activity (27% compared to Ct) and Na(+),K(+)-ATPase activity (125% compared to Ct); and 4) did not change the protein expression of the α1-subunit of Na(+),K(+)-ATPase, AT(1) and AT(2). Pre-treatment with an AT(1) receptor blocker (losartan, 10 mg/Kg) or an ACE inhibitor (enalapril, 5 mg/Kg) blocked the lead-induced increase of arterial pressure. However, a ganglionic blockade (hexamethonium, 20 mg/Kg) did not prevent lead's hypertensive effect.
Acute exposure to lead below the reference blood concentration increases systolic arterial pressure by increasing angiotensin II levels due to ACE activation. These findings offer further evidence that acute exposure to lead can trigger early mechanisms of hypertension development and might be an environmental risk factor for cardiovascular disease.
慢性铅暴露会导致高血压和心血管疾病。我们的目的是评估急性铅暴露对动脉压的影响，并阐明铅诱导高血压发展过程中的早期机制。
方法/主要发现：用醋酸铅（静脉推注剂量 320µg/Kg）处理 Wistar 大鼠，并在 120 分钟内测量收缩压、舒张压和心率。发现动脉压升高，并评估了肾素-血管紧张素系统、Na(+)、K(+)-ATP 酶和自主反射在动脉压升高中的潜在作用。在麻醉大鼠中，铅暴露：1）产生 37±1.7µg/dL 的血铅水平，低于参考血浓度（60µg/dL）；2）升高收缩压（Ct：109±3mmHg 比 Pb：120±4mmHg）；3）增加 ACE 活性（比 Ct 增加 27%）和 Na(+)、K(+)-ATP 酶活性（比 Ct 增加 125%）；和 4）不改变 Na(+)、K(+)-ATP 酶的α1 亚单位、AT(1)和 AT(2)的蛋白表达。用 AT(1)受体阻滞剂（氯沙坦，10mg/Kg）或 ACE 抑制剂（依那普利，5mg/Kg）预处理可阻断铅诱导的动脉压升高。然而，神经节阻滞剂（六烃季铵，20mg/Kg）不能阻止铅的升压作用。
低于参考血浓度的急性铅暴露通过激活 ACE 增加血管紧张素 II 水平来升高收缩压。这些发现进一步证明，急性铅暴露可引发高血压发展的早期机制，并可能成为心血管疾病的环境危险因素。
