van Zwieten P A
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
J Hypertens Suppl. 1992 Dec;10(7):S1-12.
A brief survey is given of the development of the drug therapy of essential hypertension over five decades, followed by a discussion on newer antihypertensive drugs and principles.
Virtually all levels and elements of the sympathetic nervous system can be modulated by drugs in such a manner that elevated blood pressure is lowered, for instance with the use of central alpha 2-adrenoceptor agonists (clonidine, alpha-methyldopa), ganglioplegic drugs, peripheral adrenergic neurone blockers, and alpha- and beta-adrenoceptor antagonists. The beta-blockers have been maintained as a very major group of antihypertensive therapeutics. Among alpha-adrenoceptor antagonists, only the selective alpha 1-blockers are useful as antihypertensive drugs, although some interest has developed in newer alpha 2-adrenoceptor antagonists which are selective for postsynaptic alpha 2-adrenoceptors.
Diuretics, in spite of some criticism, are still a cornerstone in antihypertensive drug treatment. Their position has been reinforced by the results of the recent Systolic Hypertension in the Elderly Program, Swedish Trial in Old Patients with Hypertension and Medical Research Council (Elderly) trials.
Calcium antagonists have been extended by several new dihydropyridines which appear to be more vasoselective than the classical compounds.
ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS: Various new ACE inhibitors have been introduced, but so far they have not clearly offered major advantages over the established compounds.
Renin inhibitors and angiotensin II-receptor antagonists are being studied for their potential as antihypertensive drugs and they are also important because they may modulate the renin-angiotensin-aldosterone system. Inhibitors of neutral endopeptidase will cause an accumulation of endogenous atrial natriuretic peptide, and hence lower blood pressure by counteracting several effects of the renin-angiotensin-system. Potassium channel openers are vasodilators and potential antihypertensive drugs with additional anti-ischaemic activity.
简要回顾五十年来原发性高血压药物治疗的发展历程，随后讨论新型抗高血压药物及治疗原则。
实际上，交感神经系统的几乎所有层面和要素都可通过药物进行调节，从而降低血压，例如使用中枢α2肾上腺素能受体激动剂（可乐定、甲基多巴）、神经节阻断药、外周肾上腺素能神经元阻滞剂以及α和β肾上腺素能受体拮抗剂。β受体阻滞剂一直是非常重要的一类抗高血压治疗药物。在α肾上腺素能受体拮抗剂中，只有选择性α1受体阻滞剂可作为抗高血压药物，不过，对新型的、对突触后α2肾上腺素能受体具有选择性的α2肾上腺素能受体拮抗剂也产生了一些兴趣。
尽管受到一些批评，但利尿剂仍是抗高血压药物治疗的基石。近期的老年收缩期高血压计划、瑞典老年高血压患者试验以及医学研究委员会（老年）试验的结果进一步巩固了它们的地位。
几种新型二氢吡啶类钙拮抗剂已问世，它们似乎比传统化合物具有更强的血管选择性。
血管紧张素转换酶（ACE）抑制剂：已推出多种新型ACE抑制剂，但到目前为止，它们并未明显显示出相对于现有药物的主要优势。
肾素抑制剂和血管紧张素II受体拮抗剂作为抗高血压药物的潜力正在研究中，它们也很重要，因为它们可能调节肾素 - 血管紧张素 - 醛固酮系统。中性内肽酶抑制剂会导致内源性心房利钠肽积聚，从而通过抵消肾素 - 血管紧张素系统的多种作用来降低血压。钾通道开放剂是血管扩张剂，也是具有额外抗缺血活性的潜在抗高血压药物。
