Neurohormonal activation and pharmacological inhibition in pulmonary arterial hypertension and related right ventricular failure
Neurohormonal activation and pharmacological inhibition in pulmonary arterial hypertension and related right ventricular failure
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DOI：
10.1007/s10741-016-9566-3
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发表时间：
2016-09-01
影响因子：
4.6
通讯作者：
Balbi, Manrico
中科院分区：
文献类型：
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作者：
Ameri, Pietro;Bertero, Edoardo;Balbi, Manrico
在过去的十年中，交感神经和肾素-血管紧张素-醛固酮系统（分别为SNS和RAAS）的过度活跃已多次与肺动脉高压（PAH）和PAH相关的右心衰（PAH- rvf）的病理生理有关，这就提出了神经激素抑制是否可以用于这些疾病的问题。实验数据表明，RAAS可能参与肺血管重构，而肺血管重构实际上被RAAS拮抗剂阻断。-受体阻滞剂对肺血管的有利作用也已被描述，即使缺乏关于-肾上腺素能受体在多环芳烃中的信息。此外，现有证据表明，SNS和RAAS对压力过载的右心室的刺激最初是代偿性的，但随着时间的推移会变得不适应。尽管与人类多环芳烃的重要差异可能限制了这些发现的转化价值，但在接受β受体阻滞剂或RAAS抑制剂治疗的多环芳烃动物模型中，RV逆转重构一直表现出来。在多环芳烃和多环芳烃裂谷热中神经激素拮抗作用的观察性研究仅有少数发表。尽管如此，在特定治疗之上的-受体阻滞剂似乎是安全的，而且可能也是有效的。矿皮质激素受体和内皮素- a受体拮抗剂的联合使用可能由于积极的药效学相互作用而产生叠加效应。虽然神经激素抑制剂目前不能推荐用于治疗多环芳烃和多环芳烃裂谷热，但它们值得进一步研究。
During the last decade, hyperactivity of the sympathetic nervous and renin-angiotensin-aldosterone systems (SNS and RAAS, respectively) has repeatedly been related to the pathophysiology of pulmonary arterial hypertension (PAH) and PAH-related right ventricular failure (PAH-RVF), raising the question of whether neurohormonal inhibition may be indicated for these conditions. Experimental data indicate that the RAAS may be involved in pulmonary vascular remodeling, which is in fact halted by RAAS antagonism. Favorable actions of beta-blockers on the pulmonary vasculature have also been described, even if information about beta-adrenergic receptors in PAH is lacking. Furthermore, the available evidence suggests that stimulation of the pressure-overloaded RV by the SNS and RAAS is initially compensatory, but becomes maladaptive over time. Consistently, RV reverse remodeling has been shown in PAH animal models treated with either beta-blockers or RAAS inhibitors, although important differences with human PAH may limit the translational value of these findings. Only few observational studies of neurohormonal antagonism in PAH and PAH-RVF have been published. Nonetheless, beta-blockers on top of specific therapy appear to be safe and possibly also effective. The combination of mineralocorticoid receptor and endothelin-A receptor antagonists may result in an additive effect because of a positive pharmacodynamic interaction. While neurohormonal inhibitors cannot be recommended at present for treatment of PAH and PAH-RVF, they are worth being further investigated.