Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice
Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice
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DOI：
10.1046/j.1365-201x.2003.01089.x
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发表时间：
2003-03-01
期刊：
影响因子：
--
通讯作者：
Kaye, D
中科院分区：
文献类型：
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作者：
Esler, M;Lambert, G;Kaye, D
目的：近年来，心血管神经科学发生了一场革命，在某些情况下，通过交感神经记录和儿茶酚胺同位素稀释方法获得的病理生理学知识转化为临床实践。肥胖相关的高血压：基于大多数模型的发现，早期的假设是肥胖体重增加的部分原因是交感神经活动不足减少了产热。微神经摄影和人类肥胖的局部去甲肾上腺素溢出测量已经推翻了这一假设，削弱了使用β(3)-肾上腺素能激动剂刺激产热的理由。指向骨骼肌血管的节后纤维交感神经放电率增加，肾脏交感神经张力增加，肾脏去甲肾上腺素溢出率增加一倍。鉴于这些发现，抗肾上腺素能降压药可能是治疗肥胖相关性高血压的首选药物，但这还没有得到充分的测试。原发性高血压：压力是否会导致高血压，这一问题此前曾引起激烈争论，但最近澳大利亚政府机构——专家医学审查委员会对这一问题进行了审查。尽管有医学上的影响，但裁决表明，压力是高血压的一个已被证实的原因。这一结论是在考虑了流行病学证据，尤其是所描述的原发性高血压的神经病理生理后得出的：(a)持续的交感神经刺激通常存在，(b)去肾上腺素能脑干神经元的球上投射被激活，(c)肾上腺素作为交感神经中的共递质释放。这些被认为是压力的生物学标记。心脏衰竭：一度，衰竭的心脏被认为是交感神经丧失。长期服用肌力肾上腺素能激动剂，以提供被认为缺乏的心脏儿茶酚胺刺激，增加死亡率。去甲肾上腺素同位素稀释方法随后证明，流向心脏的交感神经被优先激活，心脏去甲肾上腺素溢出量增加了50倍。心脏交感神经的刺激水平是死亡最有力的预测指标。这些观察结果为非常成功地引入-肾上腺素能阻滞剂治疗心力衰竭提供了理论基础。
Aim: There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology.Obesity-related hypertension: An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of beta(3)-adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post-ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity-related hypertension, but this has not been adequately tested.Essential hypertension: Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress.Cardiac failure: At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50-fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of beta-adrenergic blockers for treatment of heart failure.