Volpe Massimo, Carnovali Marino, Mastromarino Vittoria
Cardiology Department, Clinical and Molecular Medicine Department, Sapienza University of Rome, 00189 Rome, Italy IRCCS Neuromed, 86077 Pozzilli, IS, Italy
Rehabilitation Department, A.O. "G. Salvini" 20024 Garbagnate Milanese, Milan, Italy.
Clin Sci (Lond). 2016 Jan;130(2):57-77. doi: 10.1042/CS20150469.
After its discovery in the early 1980s, the natriuretic peptide (NP) system has been extensively characterized and its potential influence in the development and progression of heart failure (HF) has been investigated. HF is a syndrome characterized by the activation of different neurohormonal systems, predominantly the renin-angiotensin (Ang)-aldosterone system (RAAS) and the sympathetic nervous system (SNS), but also the NP system. Pharmacological interventions have been developed to counteract the neuroendocrine dysregulation, through the down modulation of RAAS with ACE (Ang-converting enzyme) inhibitors, ARBs (Ang receptor blockers) and mineralcorticoid antagonists and of SNS with β-blockers. In the last years, growing attention has been paid to the NP system. In the present review, we have summarized the current knowledge on the NP system, focusing on its role in HF and we provide an overview of the pharmacological attempts to modulate NP in HF: from the negative results of the study with neprilysin (NEP) inhibitors, alone or associated with an ACE inhibitor and vasopeptidase inhibitors, to the most recently and extremely encouraging results obtained with the new pharmacological class of Ang receptor and NEP inhibitor, currently defined ARNI (Ang receptor NEP inhibitor). Indeed, this new class of drugs to manage HF, supported by the recent results and a vast clinical development programme, may prompt a conceptual shift in the treatment of HF, moving from the inhibition of RAAS and SNS to a more integrated target to rebalance neurohormonal dysregulation in HF.
20世纪80年代初发现利钠肽（NP）系统后，该系统已得到广泛研究，其在心力衰竭（HF）发生和发展中的潜在影响也已被探究。HF是一种以不同神经激素系统激活为特征的综合征，主要是肾素-血管紧张素（Ang）-醛固酮系统（RAAS）和交感神经系统（SNS），但也包括NP系统。已开发出药物干预措施来对抗神经内分泌失调，通过使用ACE（血管紧张素转换酶）抑制剂、ARB（血管紧张素受体阻滞剂）和盐皮质激素拮抗剂下调RAAS，以及使用β受体阻滞剂下调SNS。近年来，人们对NP系统的关注日益增加。在本综述中，我们总结了关于NP系统的现有知识，重点关注其在HF中的作用，并概述了在HF中调节NP的药理学尝试：从单独使用或与ACE抑制剂和血管肽酶抑制剂联合使用中性肽链内切酶（NEP）抑制剂的研究负面结果，到使用新型血管紧张素受体和NEP抑制剂（目前定义为ARNI，血管紧张素受体NEP抑制剂）获得的最新且极其令人鼓舞的结果。事实上，这一新型治疗HF的药物，在近期结果和广泛的临床开发计划支持下，可能促使HF治疗发生概念转变，从抑制RAAS和SNS转向更综合的靶点，以重新平衡HF中的神经激素失调。
