选择性盐皮质激素受体拮抗剂是否迎来了新的曙光？
Is there a new dawn for selective mineralocorticoid receptor antagonism?
作者信息
Luther James M
机构信息
Divisions of Clinical Pharmacology and Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
出版信息
Curr Opin Nephrol Hypertens. 2014 Sep;23(5):456-61. doi: 10.1097/MNH.0000000000000051.
PURPOSE OF REVIEW
Aldosterone and the mineralocorticoid receptor contribute to resistant hypertension and cardiovascular mortality, and mineralocorticoid receptor antagonists effectively reduce these complications. Their use is limited in certain populations with a higher risk of hyperkalemia or renal dysfunction. This review will highlight recent developments in extra-renal mineralocorticoid receptor research and the development of novel mineralocorticoid receptor antagonists.
RECENT FINDINGS
Tissue-specific knockout-out models provide definitive evidence that the vascular mineralocorticoid receptor directly contributes to hypertension and vascular remodeling, independent of renal effects. Several nonsteroidal mineralocorticoid receptor antagonists are in preclinical development or early-stage clinical trials. Several nonsteroidal mineralocorticoid receptor antagonists have demonstrated preserved cardiovascular benefit with a reduced incidence of hyperkalemia in preclinical studies.
SUMMARY
Novel, potent nonsteroidal mineralocorticoid receptor antagonists are in development, although their effect on cardiovascular and adverse drug events requires further investigation.
综述目的
醛固酮和盐皮质激素受体与顽固性高血压及心血管疾病死亡率相关，盐皮质激素受体拮抗剂可有效降低这些并发症。但在某些高钾血症或肾功能不全风险较高的人群中，其应用受到限制。本综述将重点介绍肾外盐皮质激素受体研究的最新进展以及新型盐皮质激素受体拮抗剂的研发情况。
最新发现
组织特异性敲除模型提供了确凿证据，表明血管盐皮质激素受体直接导致高血压和血管重塑，与肾脏效应无关。几种非甾体类盐皮质激素受体拮抗剂正处于临床前开发或早期临床试验阶段。在临床前研究中，几种非甾体类盐皮质激素受体拮抗剂已证明在降低高钾血症发生率的同时，仍保留心血管益处。
总结
新型强效非甾体类盐皮质激素受体拮抗剂正在研发中，但其对心血管和不良药物事件的影响仍需进一步研究。
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