Is there a new dawn for selective mineralocorticoid receptor antagonism?
Is there a new dawn for selective mineralocorticoid receptor antagonism?
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DOI：
10.1097/mnh.0000000000000051
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发表时间：
2014-09
影响因子：
3.2
通讯作者：
Luther JM
中科院分区：
文献类型：
--
作者：
Luther JM
醛固酮和矿化皮质激素受体可导致顽固性高血压和心血管疾病死亡率，而矿化皮质激素受体拮抗剂可有效减少这些并发症。在某些高钾血症或肾功能不全风险较高的人群中，它们的使用受到限制。本文将重点介绍肾外矿糖皮质激素受体的研究进展和新型矿糖皮质激素受体拮抗剂的开发。组织特异性敲除模型提供了明确的证据，血管矿化皮质激素受体直接参与高血压和血管重塑，独立于肾脏作用。几种非甾体矿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MR拮抗剂显示出保留心血管益处，降低了高钾血症的发生率。新型有效的非甾体MR拮抗剂正在开发中，尽管它们对心血管和药物不良事件的影响有待进一步研究。
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. Tissue-specific knockout-out models provide definitive evidence that vascular mineralocorticoid receptor directly contributes to hypertension and vascular remodeling, independent of renal effects. Several non-steroidal mineralocorticoid receptor antagonists are in pre-clinical development or early-stage clinical trials. Several non-steroidal MR antagonists have demonstrated preserved cardiovascular benefit with a reduced incidence of hyperkalemia in pre-clinical studies. Novel, potent non-steroidal MR antagonists are in development, although their effect on cardiovascular and adverse drug events requires further investigation.