Is there a new dawn for selective mineralocorticoid receptor antagonism?

Curr Opin Nephrol Hypertens. 2014 Sep;23(5):456-61. doi: 10.1097/MNH.0000000000000051.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects*
  • Blood Vessels / drug effects*
  • Blood Vessels / metabolism
  • Blood Vessels / physiopathology
  • Drug Design
  • Humans
  • Hyperkalemia / chemically induced
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Receptors, Mineralocorticoid / drug effects*
  • Receptors, Mineralocorticoid / metabolism
  • Risk Factors
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Mineralocorticoid Receptor Antagonists
  • Receptors, Mineralocorticoid