Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy.
Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy.
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DOI：
10.1002/ejhf.656
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发表时间：
2017-02
影响因子：
18.2
通讯作者：
Díez J
中科院分区：
文献类型：
--
作者：
Díez J
利钠肽(NPs)可促进慢性心力衰竭(CHF)早期的利尿、利钠和血管扩张，对抗肾素-血管紧张素-醛固酮系统(RAAS)和交感神经系统(SNS)的过度刺激。尽管随着心力衰竭的进展，循环中的NP浓度急剧增加，但它们的影响变得迟钝。与对照组相比，服用外源性心房利钠肽(ANP)或脑钠尿肽(BNP)后，晚期CHF患者利尿、利钠和血管扩张的增加有所减轻。几个主要因素可能解释了心力衰竭时利钠肽系统(NPS)疗效降低的原因。首先，主动形式的NPs的可获得性减少，即BNP。第二，靶器官的反应性减弱。第三，RAAS和SNS的反调节激素以及内皮素-1被过度激活。因此，近年来一直在探索提高NPS在CHF中的功能有效性的药理学方法。就临床结果而言，由于几个原因，关于合成BNP或单独使用奈普利辛抑制剂或与血管紧张素转换酶抑制剂联合使用的研究一直存在争议。然而，最近，血管紧张素受体neprilysin抑制剂saubitril/valsartan取得了令人鼓舞的结果。现有数据显示，萨舒比利/valsartan治疗与NPs及其细胞内介质环鸟苷一磷酸水平的增加有关，这表明NPS的功能有效性得到改善，此外还对死亡率和发病率结果产生有利影响。因此，NPS和RAAS与萨舒比利/valsartan联合靶向治疗是目前纠正CHF神经激素失衡的最佳方法。
Natriuretic peptides (NPs) promote diuresis, natriuresis and vasodilation in early chronic heart failure (CHF), countering renin–angiotensin–aldosterone system (RAAS) and sympathetic nervous system (SNS) overstimulation. Despite dramatic increases in circulating NP concentrations as CHF progresses, their effects become blunted. Increases in diuresis, natriuresis, and vasodilation after administration of exogenous atrial (ANP) or brain (BNP) natriuretic peptides are attenuated in patients with advanced CHF compared with controls. Several major factors may account for the reduced effectiveness of the natriuretic peptide system (NPS) in CHF. First, there is reduced availability of active forms of NPs, namely BNP. Second, target organ responsiveness becomes diminished. Third, the counter‐regulatory hormones of the RAAS and SNS, and endothelin‐1 become over‐activated. Therefore, pharmacological approaches to enhance the functional effectiveness of the NPS in CHF have been explored in recent years. In terms of clinical outcomes, studies of synthetic BNP, or of neprilysin inhibitors alone or associated with an angiotensin converting enzyme inhibitor, have been controversial for several reasons. Recently, however, encouraging results have been obtained with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan. The available data show that treatment with sacubitril/valsartan is associated with increased levels of NPs and their intracellular mediator cyclic guanosine monophosphate, suggesting improved functional effectiveness of the NPS, in addition to beneficial effects on mortality and morbidity outcomes. Therefore, combined targeting of the NPS and RAAS with sacubitril/valsartan emerges as the current optimal approach for redressing the neurohormonal imbalance in CHF.