Haeusler G
Department of Pharmaceutical Research and Development E. Merck, Darmstadt, F.R.G.
Eur Heart J. 1987 Dec;8 Suppl M:135-42. doi: 10.1093/eurheartj/8.suppl_m.135.
Since an understanding of the pathogenesis of essential hypertension is unlikely to be imminent, there is little chance that antihypertensive therapy will become curative in the near future. What progress can be expected in symptomatic therapy? In the past, nearly all major mechanisms involved in the regulation of blood pressure have become targets of antihypertensive drugs; they include the sympathetic neuro-effector system, neuronal substrates of central cardiovascular regulation, the kidney, the renin angiotensin aldosterone system and the vascular smooth muscle cell. Among drugs that influence the function of the sympathetic nervous system, the clinical potential of one mechanism of action has not yet been explored: it is the inhibition of noradrenaline release through stimulation of inhibitory receptors located at the adrenergic nerve terminals of the cardiovascular system (inhibitory presynaptic receptors). Among the multiple presynaptic receptors, dopamine receptors appear to be a particularly interesting target. The not entirely expected activity of angiotensin converting enzyme (ACE) inhibitors in essential hypertension prompted the search for renin inhibitors. Whether interruption of the cascade of the renin angiotensin system at the first reaction step by renin inhibitors, as compared to the interference at the second step by ACE inhibitors, will yield relevant progress in antihypertensive drug therapy remains to be seen.
由于原发性高血压的发病机制近期不太可能被完全理解,降压治疗在不久的将来治愈该病的可能性很小。在症状性治疗方面可以期待取得哪些进展呢?过去,几乎所有参与血压调节的主要机制都已成为降压药物的作用靶点;这些机制包括交感神经效应系统、中枢心血管调节的神经基质、肾脏、肾素 - 血管紧张素 - 醛固酮系统以及血管平滑肌细胞。在影响交感神经系统功能的药物中,有一种作用机制的临床潜力尚未得到探索:即通过刺激位于心血管系统肾上腺素能神经末梢的抑制性受体(抑制性突触前受体)来抑制去甲肾上腺素的释放。在多种突触前受体中,多巴胺受体似乎是一个特别有趣的靶点。血管紧张素转换酶(ACE)抑制剂在原发性高血压中表现出不完全预期的活性,这促使人们寻找肾素抑制剂。与ACE抑制剂在第二步进行干预相比,肾素抑制剂在第一步反应中断肾素 - 血管紧张素系统级联反应是否会在降压药物治疗中取得相关进展,仍有待观察。