Cleophas T J
Department of Medicine, Merwede Hospital, Dordrecht, Netherlands.
Am J Ther. 1998 Nov;5(6):413-9. doi: 10.1097/00045391-199811000-00010.
In clinical practice it is far from uncommon that antihypertensive drugs fail to meet their expectations. This is mainly due to mechanisms counteracting their antihypertensive effects. These mechanisms include stimulation of the sympathetic nervous system (SNS), inhibition of the parasympathetic nervous system (PSNS), stimulation of the renin-angiotensin-aldosterone system (RAAS), as well as endothelium-dependent mechanisms. To review whether the activation of such mechanisms follows differential patterns depending on the type of antihypertensive therapy being used. The antihypertensive effects of diuretics and calcium channel blockers are largely offset by all of the mechanisms enumerated. The antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II (AII) receptor antagonists and beta-blockers are counteracted by all of the mechanisms enumerated except for the effects of a stimulated RAAS and SNS, respectively. ACE inhibitors/AII receptor antagonists and beta-blockers display a better profile of mechanisms counteracting their antihypertensive effects than other categories of drugs currently available. However, because this is not routinely confirmed by random trial evidence, additional determinants of drug performance must be considered including between-subject disparities in drug response, metabolic effects, and proliferative effects.
在临床实践中，抗高血压药物未能达到预期效果的情况屡见不鲜。这主要是由于一些机制抵消了它们的降压作用。这些机制包括交感神经系统（SNS）的激活、副交感神经系统（PSNS）的抑制、肾素-血管紧张素-醛固酮系统（RAAS）的激活以及内皮依赖性机制。旨在探讨这些机制的激活是否因所使用的抗高血压治疗类型而异。利尿剂和钙通道阻滞剂的降压作用在很大程度上被上述所有机制抵消。血管紧张素转换酶（ACE）抑制剂/血管紧张素II（AII）受体拮抗剂和β受体阻滞剂的降压作用分别被除激活的RAAS和SNS作用之外的上述所有机制抵消。与目前可用的其他类别药物相比，ACE抑制剂/AII受体拮抗剂和β受体阻滞剂在抵消其降压作用的机制方面表现更佳。然而，由于随机试验证据并未常规证实这一点，因此必须考虑药物性能的其他决定因素，包括个体间药物反应差异、代谢效应和增殖效应。
