Struthers A D, Dollery C T
Eur J Clin Pharmacol. 1985;28 Suppl:3-11. doi: 10.1007/BF00543703.
Much of our knowledge about the CNS control of blood pressure is derived from animal studies using techniques such as intracerebroventricular administration of drugs, stereotactic ablation of specific brain nuclei, and biochemical analysis of these nuclei. These methods have identified numerous specific brain nuclei in the brain stem and a meshwork of interconnecting neurones involved in cardiovascular control. The main neurotransmitter involved is noradrenaline but recent interest has focused on several laterally situated nuclei which are capable of synthesizing adrenaline. Centrally acting antihypertensive drugs are thought to act by stimulating central alpha 2-adrenoceptors either by the parent drug itself (clonidine) or via the formation of an active metabolite (alpha-methyldopa). This leads to decreased peripheral sympathetic activity and a hypotensive response but the latter is often attained at the expense of central side-effects such as drowsiness or dry mouth. The mechanism of the antihypertensive effect of beta-blockers remains uncertain although the balance of evidence is against a central effect. The central administration of propranolol causes decreased peripheral sympathetic activity in animals, but plasma catecholamine levels are little altered by beta-blockers in man. In equipotent antihypertensive doses, central alpha-agonists cause a much greater reduction in plasma noradrenaline than beta-blockers.
我们关于中枢神经系统对血压控制的许多知识都来自动物研究，这些研究采用了诸如脑室内给药、特定脑核的立体定向损毁以及对这些核的生化分析等技术。这些方法已确定脑干中有许多特定的脑核以及参与心血管控制的相互连接的神经元网络。主要涉及的神经递质是去甲肾上腺素，但最近的研究兴趣集中在几个能够合成肾上腺素的位于外侧的核上。中枢性抗高血压药物被认为是通过母体药物本身（可乐定）或通过形成活性代谢物（α-甲基多巴）来刺激中枢α2-肾上腺素受体而发挥作用的。这会导致外周交感神经活动降低和血压下降反应，但后者往往是以出现诸如嗜睡或口干等中枢副作用为代价的。β受体阻滞剂的降压作用机制仍不确定，尽管证据的天平倾向于其没有中枢作用。在动物中，普萘洛尔的中枢给药会导致外周交感神经活动降低，但在人类中，β受体阻滞剂对血浆儿茶酚胺水平几乎没有影响。在等效的降压剂量下，中枢α激动剂比β受体阻滞剂能使血浆去甲肾上腺素水平降低得更多。
