Remme W J
Sticares, Cardiovascular Research Foundation, Rotterdam, The Netherlands.
Eur Heart J. 1995 Dec;16 Suppl N:73-8. doi: 10.1093/eurheartj/16.suppl_n.73.
Angiotensin converting enzyme (ACE) inhibition undoubtedly has become the cornerstone of heart failure treatment. Useful in each stage, it should possibly be considered first-line treatment in many patients with mild heart failure in whom fluid retention is not clearly present. Careful consideration of the optimal dose for the individual is important. Until further data are available concerning the efficacy and tolerability of high and low doses, the clinician should consider the target doses used in large controlled heart failure trials. Even under optimal dosing conditions, it is likely that ACE inhibition may not suffice in completely modulating the extensive neurohormonal stimulation extant in heart failure. In part this may result from a breakthrough of the ACE inhibitor effect as well as from activation of hormones and peptides that may not be affected by ACE inhibition. Also, a substantial proportion of patients may not tolerate sufficient ACE inhibition. Alternative or additional therapy aimed at modulating neurohormonal activation concerns interference with other parts of the renin angiotensin system, such as angiotensin II receptor and aldosterone receptor antagonism. Sympathetic activity and catecholamine levels may decrease with dopaminergic D2 agonists and, possibly, beta-blockade; in the latter, this may be confined to patients with pre-existing sympathetic over-activation. Increasing circulating levels of atrial natriuretic peptide via neutral endopeptidase inhibition may offer an alternative way to increase diuresis and natriuresis without neuroendocrine stimulation. Novel possibilities that have not yet been tested sufficiently in patients with heart failure include endothelin receptor antagonism, arginine vasopressin antagonism, and renin inhibition. Finally, digitalis glycosides may be considered neurohormonal modulators in addition to being positive inotropes. Heart failure is a complex condition that involves many organs and systems besides the heart. Polypharmacy tailored to the individual is mandatory. It is thus necessary to investigate approaches to the modulation of neurohormonal activation beyond ACE inhibition.
血管紧张素转换酶（ACE）抑制无疑已成为心力衰竭治疗的基石。它在每个阶段都有用，对于许多无明显液体潴留的轻度心力衰竭患者，可能应被视为一线治疗。仔细考虑个体的最佳剂量很重要。在有关于高剂量和低剂量的疗效及耐受性的更多数据可用之前，临床医生应考虑大型对照心力衰竭试验中使用的目标剂量。即使在最佳给药条件下，ACE抑制也可能不足以完全调节心力衰竭中存在的广泛神经激素刺激。部分原因可能是ACE抑制剂作用的突破以及可能不受ACE抑制影响的激素和肽的激活。此外，相当一部分患者可能无法耐受足够的ACE抑制。旨在调节神经激素激活的替代或附加疗法涉及干扰肾素血管紧张素系统的其他部分，如血管紧张素II受体和醛固酮受体拮抗。多巴胺能D2激动剂以及可能的β受体阻滞剂可降低交感神经活性和儿茶酚胺水平；对于后者，这可能仅限于已有交感神经过度激活的患者。通过抑制中性内肽酶增加心房利钠肽的循环水平可能提供一种在无神经内分泌刺激的情况下增加利尿和利钠的替代方法。在心力衰竭患者中尚未得到充分测试的新可能性包括内皮素受体拮抗、精氨酸加压素拮抗和肾素抑制。最后，洋地黄苷除了是正性肌力药外，还可被视为神经激素调节剂。心力衰竭是一种复杂的病症，除心脏外还涉及许多器官和系统。必须根据个体情况进行联合用药。因此，有必要研究除ACE抑制之外调节神经激素激活的方法。
