Chai S S, Webb R C
Department of Physiology, University of Michigan, Ann Arbor 48109.
Environ Health Perspect. 1988 Jun;78:85-9. doi: 10.1289/ehp.887885.
Considerable controversy exists concerning the possible role of lead in the etiology of human hypertension. In animal studies, there is convincing evidence that lead alters cardiovascular responsiveness; rats drinking water containing 100 ppm lead develop a chronic, significant 15 to 20 mm Hg elevation in systolic blood pressure. Pressor responsiveness to catecholamines is enhanced in animals chronically exposed to lead, and the responsiveness of isolated vascular smooth muscle to adrenergic agonists is increased in rats with lead-induced hypertension. Experimental evidence suggests that alterations in the cellular mechanisms that regulate intracellular calcium concentration may contribute to the abnormal vascular function in lead-induced hypertension. Recent work in our laboratory indicates that increased vascular reactivity in genetic hypertension is associated with altered activity of the protein kinase C branch of the calcium messenger system. Contractile responses to lead in rabbit mesenteric artery are potentiated by activators (phorbol esters) of this enzyme complex, and a selective inhibitor of protein kinase C inhibited contractions induced by lead. Based on these results, it is proposed that a cellular component of the action of lead to increase vascular reactivity may relate to the role of protein kinase C in smooth muscle contraction.
关于铅在人类高血压病因学中可能扮演的角色，存在相当大的争议。在动物研究中，有确凿证据表明铅会改变心血管反应性；饮用含100 ppm铅的水的大鼠会出现慢性、显著的收缩压升高15至20毫米汞柱。长期接触铅的动物对儿茶酚胺的升压反应增强，而在铅诱导的高血压大鼠中，离体血管平滑肌对肾上腺素能激动剂的反应性增加。实验证据表明，调节细胞内钙浓度的细胞机制改变可能导致铅诱导的高血压中血管功能异常。我们实验室最近的研究表明，遗传性高血压中血管反应性增加与钙信使系统蛋白激酶C分支的活性改变有关。该酶复合物的激活剂（佛波酯）可增强兔肠系膜动脉对铅的收缩反应，而蛋白激酶C的选择性抑制剂可抑制铅诱导的收缩。基于这些结果，有人提出铅增加血管反应性作用的细胞成分可能与蛋白激酶C在平滑肌收缩中的作用有关。
