Catcholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment
Catcholamine and nitric oxide systems as targets of chronic lead exposure in inducing selective functional impairment
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DOI：
10.1016/s0024-3205(00)00954-1
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发表时间：
2000-12-15
期刊：
影响因子：
6.1
通讯作者：
Felaco, M
中科院分区：
文献类型：
--
作者：
Carmignani, M;Volpe, AR;Felaco, M
大鼠在饮用水中暴露于60 ppm的铅（铅，作为醋酸盐）10个月，以进一步评估慢性铅暴露对心血管的影响。治疗结束时，对照大鼠血铅平均值为3.1+/-0.3马克/分升，铅暴露大鼠血铅平均值为22.8+/-1.2马克/分升（平均+/-SE，每组n=12）；这些价值不能与人类的价值相比。铅能显著提高血浆去甲肾上腺素（NA）和肾上腺素(A)水平，但对左旋多巴和多巴胺水平无显著影响；铅增加了单氨基氧化酶活性，主要在主动脉和肝脏；在暴露于铅的脂肪中，主动脉、肝脏、心脏和肾脏显示出离散的组织病理学改变，其中血浆中一氧化氮（NO，测定为l -瓜氨酸）水平降低。铅能够诱导高血压，导致心脏肌力的增加，主要是外周总阻力的增加。我们还讨论了这些数据与我们以前的研究中获得的数据，这些研究是在大鼠中进行的，大鼠暴露于饮用水中的铅（15-60 ppm），时间从5个月到18个月不等。铅似乎通过中枢机制（从而增加血浆NA和A）和环磷酸腺苷（cAMP）依赖性钙离子（Ca++）在血管和心肌细胞中的收缩机制(也通过增加血管α（2)-和心肌β(1)-肾上腺素受体的反应性）增加交感神经活动。血浆NO的减少，有助于血管阻力和心脏肌力的增加，被解释为铅对钾likk -kinin （KK）和肾素-血管紧张素-醛固酮（RAA）系统相关酶活性的作用的结果。结论：慢性铅暴露可影响选择性神经内分泌（如：神经内分泌）。（如儿茶酚胺）、自通道（如KK和RAA）和转导通路（如cAMP、NO、ca++）参与心血管功能。(C) 2000 Elsevier Science Inc.；版权所有。
Rats were exposed for ten months to 60 ppm of lead (Pb, as acetate) in drinking water to further assess cardiovascular effects of chronic Pb exposure. At the end of the treatment, mean blood Pb was 3.1+/-0.3 mug/dL in the control rats and 22.8+/-1.2 mug/dL in the Pb-exposed rats (means+/-SE, n=12 in each group); these values were not comparable to those of humans. Pb greatly increased plasma levels of noradrenaline (NA) and adrenaline (A), but not those of L-DOPA and dopamine; monoaminoxidase activity was augmented by Pb, mostly in the aorta and in the liver; the aorta, liver, heart and kidney showed discrete histopathological alterations in the Pb-exposed fats, in which plasma levels of nitric oxide (NO, determined as L-citrulline) were reduced. Pb was able to induce blood hypertension, resulting from increase of cardiac inotropism and, mostly, total peripheral resistance. These data were discussed also in relation to those obtained in our previous studies carried out in rats exposed to Pb in drinking water (15-60 ppm) for periods ranging from five to eighteen months. Pb appeared to increase both sympathetic nerve activity by central mechanisms (thus increasing plasma NA and A) and cyclic adenosine monophosphate (cAMP)-dependent availability of calcium ions (Ca++) for contractile mechanisms in the vascular and cardiac myocells (also through an increased vascular alpha (2)- and myocardial beta (1)-adrenoreceptor reactivity). The reduction of plasma NO, contributing to increase vascular resistance and cardiac inotropism, was explained as a result of actions of Pb on enzyme activities concerned with the kallikrein-kinin (KK) and renin-angiotensin-aldosterone (RAA) systems. It was concluded that chronic Pb exposure is able to affect selective neuroendocrine (i,e., catecholamine), autacoidal (i.e., KK and RAA) and transductional pathways (i.e., cAMP, NO, Ca++) involved in the cardiovascular function. (C) 2000 Elsevier Science Inc. All rights reserved.