title: Is there a new dawn for selective mineralocorticoid receptor antagonism?
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Novel, potent nonsteroidal mineralocorticoid receptor antagonists are in development, although their effect on cardiovascular and adverse drug events requires further investigation.
authors.affiliation: Divisions of Clinical Pharmacology and Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Luther
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects* / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid