Costello-Boerrigter Lisa C, Boerrigter Guido, Burnett John C
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Med Clin North Am. 2003 Mar;87(2):475-91. doi: 10.1016/s0025-7125(02)00181-5.
Diuretics continue to be a mainstay in patients with CHF. Conventional diuretic therapy is associated, however, with potentially deleterious neurohumoral activation and renal impairment. It is not known to what extent these neurohumoral effects are offset by concurrent therapy with ACE-I, beta-blockers, and other agents. In the past, there was no alternative to conventional diuretic therapy, so their potential for adverse outcome in the long term could not be assessed. Enhancement of the natriuretic peptide system could provide us with a better strategy to treat sodium and water retention. In a unique way, the natriuretic peptides combine several of the beneficial actions of the other diuretics, but without the associated cost. Natriuretic peptides, like conventional diuretics, are natriuretic and diuretic. There are important differences, however. First, unlike conventional diuretics, NPs do not activate RAAS. Activation of this system is associated with progression of CHF. Second, NPs inhibit the sympathetic nervous system, the activation of which is associated with heart failure progression, myocyte necrosis and apoptosis, and arrhythmias. Third, unlike conventional diuretics that lead to a decrease in GFR by reflex mechanisms. NPs maintain or even improve GFR. We now appreciate that some "old" drugs may be beneficial to CHF patients in a new way, as is the case with spironolactone. The survival benefit of this aldosterone antagonist is clear: its usefulness, however, may be more a result of both its antifibrotic actions in addition to its tradional role as a potassium-sparing and natriuretic agent. It is hoped that the SARAs will provide the same survival benefit, but with fewer of the sex-steroid side effects. In addition, AVP-receptor antagonists may become useful tools in the treatment of patients with hyponatremia. Likewise, the A1 AR antagonists may find a role in the CHF armamentarium by providing good diuresis and natriuresis while at the same time maintaining GFR through inhibition of TGF. Many questions remain unanswered, and studies are needed to demonstrate that the positive results seen in basic research translate into improved morbidity and mortality.
利尿剂仍然是治疗慢性心力衰竭（CHF）患者的主要药物。然而，传统的利尿治疗会引发潜在有害的神经体液激活和肾功能损害。目前尚不清楚这些神经体液效应在多大程度上会被同时使用的血管紧张素转换酶抑制剂（ACE-I）、β受体阻滞剂及其他药物所抵消。过去，除了传统的利尿治疗别无他法，因此无法评估其长期导致不良后果的可能性。增强利钠肽系统可能为我们提供一种更好的治疗钠水潴留的策略。利钠肽以独特的方式结合了其他利尿剂的多种有益作用，但没有相关的副作用。利钠肽与传统利尿剂一样，具有利钠和利尿作用。然而，它们存在重要差异。首先，与传统利尿剂不同，利钠肽不会激活肾素-血管紧张素-醛固酮系统（RAAS）。该系统的激活与CHF的进展相关。其次，利钠肽抑制交感神经系统，其激活与心力衰竭进展、心肌细胞坏死和凋亡以及心律失常相关。第三，与通过反射机制导致肾小球滤过率（GFR）降低的传统利尿剂不同，利钠肽可维持甚至提高GFR。我们现在认识到，一些“老”药物可能以新的方式对CHF患者有益，螺内酯就是如此。这种醛固酮拮抗剂的生存获益是明确的：然而，其效用可能更多是由于其抗纤维化作用以及作为保钾和利钠药物的传统作用。希望选择性醛固酮受体拮抗剂（SARAs）能提供相同的生存获益，但减少性类固醇副作用。此外，精氨酸加压素（AVP）受体拮抗剂可能成为治疗低钠血症患者的有用工具。同样，A1肾上腺素能受体（A1 AR）拮抗剂可能通过提供良好的利尿和利钠作用，同时通过抑制转化生长因子（TGF）维持GFR，在CHF治疗药物中发挥作用。许多问题仍未得到解答，需要进行研究以证明基础研究中看到的确切结果能转化为发病率和死亡率的改善。
