title: Cardiovascular effects of aldosterone: insight from adult carriers of mineralocorticoid receptor mutations.
abstract: BACKGROUND
  High plasma aldosterone has deleterious cardiovascular effects that are independent of blood pressure, but the role of the mineralocorticoid receptor remains unclear. Renal pseudohypoaldosteronism type 1 is a rare autosomal-dominant disease caused by NR3C2 loss-of-function mutations, which is characterized by renal salt loss and compensatory high renin and aldo secretion. We aimed to assess the cardiovascular outcomes in adults carrying NR3C2 mutations.
  
  
  RESULTS
  In this case-control study, 39 NR3C2 mutation carriers were compared with sex- and age-paired noncarriers. Patients underwent cardiac and vascular ultrasound, cardiac MRI with gadolinium injection, measurement of pulse wave velocity, extracellular water, 24-hour ambulatory blood pressure, and autonomous nervous system activity. Mutation carriers showed increased aldo and renin plasma levels (4.5- and 1.6-fold, respectively; P<0.0001), together with increased salt appetite (1.8-fold; P=0.002), with normal extracellular water and blood pressure, and no autonomous nervous system activation. Cardiac and vascular parameters were not significantly different between mutation carriers and noncarriers (no left ventricular remodeling or fibrosis, normal left ventricular systolic function, and aorta stiffness). Tissue Doppler showed better diastolic left ventricular function in mutation carriers (e', P=0.001; E/e', P=0.003). Mutation carriers had significantly more frequent history of slow body weight recovery at birth, symptomatic hypotension, and miscarriage in women.
  
  
  CONCLUSIONS
  Despite life-long increase in plasma aldosterone and renin levels, no adverse cardiovascular outcome occurred in pseudohypoaldosteronism type 1, but rather an improved diastolic left ventricular function. This suggests that the cardiovascular consequences of aldosterone excess require full mineralocorticoid receptor signaling.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov; unique identifier: NCT00646828.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, Paris, France. brigitte.escoubet@inserm.fr
authors.forename: Brigitte
authors.initials: B
authors.lastname: Escoubet
authors.forename: Camille
authors.initials: C
authors.lastname: Couffignal
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Laisy
authors.forename: Laurence
authors.initials: L
authors.lastname: Mangin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chillon
authors.forename: Cédric
authors.initials: C
authors.lastname: Laouénan
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Serfaty
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.forename: France
authors.initials: F
authors.lastname: Mentré
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000097:blood*; D001794:Blood Pressure; D001823:Body Composition; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011546:Pseudohypoaldosteronism / Q000235:genetics*; D011859:Radiography; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D055815:Young Adult
chemical_list: D004573:Electrolytes; C561839:NR3C2 protein, human; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D012964:Sodium; D012083:Renin
keywords: aldosterone; mutation; pseudohypoaldosteronism; receptors, mineralocorticoid; rennin–angiotensin system