Abrams W B
Hypertension. 1984 Sep-Oct;6(5 Pt 2):II87-93. doi: 10.1161/01.hyp.6.5_pt_2.ii87.
This symposium reviewed the fundamental principles, pharmacology, and clinical pharmacology of central alpha-adrenergic blood pressure regulating mechanisms. Fundamental principles Arterial baro- and chemoreceptor signals reach the nucleus of the tractus solitarius (NTS) via vagal and glossopharyngeal afferents. The NTS communicates with sympathetic preganglionic neurons in the spinal cord via centers and tracts in the medulla, pons, and hypothalamus that include an alpha-adrenergic inhibitory network. Descending tracts emphasized in this symposium originate in the C-1 epinephrine cells of the medulla, B-1 and B-3 serotonin cells of the medulla, and A-5 norepinephrine cells of the pons. Transmitters involved are norepinephrine, epinephrine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Catecholamine enzymes share protein domains in their primary structures and may be coded by linked or single genes. New methods of purifying and locating alpha- and beta-receptors have been developed. Pharmacology Methyldopa, clonidine, and clonidine-like drugs lower blood pressure by stimulating postsynaptic alpha 2-receptors in a brain stem inhibitory network, which down-regulates these receptors. Alpha 1-receptors were found to be higher in normotensive than in hypertensive rats and were increased in the latter by methyldopa administration. Alpha 2-receptors were found to differ in various tissues, which permits the development of highly selective agonists and antagonists. Although alpha-methylnorepinephrine is probably the principal metabolite of methyldopa, alpha-methylepinephrine and alpha-methyldopamine may also contribute. The site of action usually is identified as the NTS. Possible roles for the descending tracts were suggested. Clinical pharmacology Methyldopa, clonidine, guanfacine, and related drugs lower blood pressure principally by CNS mechanisms but peripheral actions may also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)
本次研讨会回顾了中枢α-肾上腺素能血压调节机制的基本原理、药理学及临床药理学。基本原理 动脉压力感受器和化学感受器信号经迷走神经和舌咽神经传入纤维到达孤束核（NTS）。NTS通过延髓、脑桥和下丘脑的中枢及传导束与脊髓中的交感神经节前神经元进行交流，其中包括一个α-肾上腺素能抑制网络。本次研讨会重点讨论的下行传导束起源于延髓的C-1肾上腺素能细胞、延髓的B-1和B-3 5-羟色胺能细胞以及脑桥的A-5去甲肾上腺素能细胞。涉及的递质有去甲肾上腺素、肾上腺素、5-羟色胺、谷氨酸和γ-氨基丁酸（GABA）。儿茶酚胺酶在其一级结构中具有共同的蛋白质结构域，可能由连锁或单个基因编码。已开发出纯化和定位α-和β-受体的新方法。药理学 甲基多巴、可乐定及可乐定类药物通过刺激脑干抑制网络中的突触后α2受体来降低血压，这会使这些受体下调。发现正常血压大鼠的α1受体比高血压大鼠的更高，甲基多巴给药后后者的α1受体增加。发现α2受体在不同组织中存在差异，这使得开发高选择性激动剂和拮抗剂成为可能。尽管α-甲基去甲肾上腺素可能是甲基多巴的主要代谢产物，但α-甲基肾上腺素和α-甲基多巴胺也可能起作用。作用部位通常被确定为NTS。有人提出了下行传导束的可能作用。临床药理学 甲基多巴、可乐定、胍法辛及相关药物主要通过中枢神经系统机制降低血压，但外周作用也可能有贡献。（摘要截选至250词）
