title: Biochemical and genetic characterization of 11 beta-hydroxysteroid dehydrogenase type 2 in low-renin essential hypertensives.
abstract: BACKGROUND
  The 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) catalyzes the conversion of cortisol (F) to cortisone (E), avoiding the interaction of cortisol with the mineralocorticoid receptor. If it fails, cortisol will stimulate sodium and water reabsorption, increasing the intravascular volume that suppresses renin and secondarily increase the blood pressure.
  
  
  OBJECTIVE
  To look for the possible contribution of a decreased ability of 11betaHSD2 to convert cortisol to its inactive metabolite cortisone in the pathogenesis of low renin hypertension (LREH).
  
  
  METHODS
  We studied 64 LREH patients (plasma renin activity, PRA < 1 ng/ml per h), eighty normo-renin essential hypertensives (NREH) (PRA: 1-2.5 ng/ml per h) and 74 normotensives. Serum aldosterone (SA), F, E and serum F/E ratio was determined in all patients. A serum F/E ratio was considered high when it was higher than X + 2SD from the normotensive value. Cytosine-adenine (CA)-repeat microsatellite region in intron 1 of HSD11B2 gene was genotyped in all patients and normotensives volunteers. In 13 LREH with high F/E ratio we performed HSD11B2 gene sequencing.
  
  
  RESULTS
  LREH had serum F/E ratio higher than NREH and normotensive controls (3.6 (2.9-4.3) versus 2.9 (2.2-4.3) versus 3.0 (2.4-3.7) (P = 0.004), respectively). We observed an inverse relation between F/E ratio and SA and PRA. In NREH and normotensives we did not find correlation between these variables. In the LREH subset the longer 155 bp CA-allele showed the highest serum F/E ratio. No mutations in coding region or short introns were found in LREH patients.
  
  
  CONCLUSIONS
  In this study we show that low-renin essential hypertensives had increased serum cortisol/cortisone ratios as compared with normotensive subjects. This suggest that some essential hypertensives, with suppressed renin activity, may have an impairment in the cortisol inactivation catalyzed by the enzyme 11betaHSD2, whose low activity in LREH patients could be associated with the length of CA-repeat microsatellite in intron 1 of the HSD11B2 gene.
authors.affiliation: Department of Endocrinology and Metabolism, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Carvajal
authors.forename: Damián G
authors.initials: DG
authors.lastname: Romero
authors.forename: Lorena M
authors.initials: LM
authors.lastname: Mosso
authors.forename: Alexis A
authors.initials: AA
authors.lastname: González
authors.forename: Carmen
authors.initials: C
authors.lastname: Campino
authors.forename: Joaquín
authors.initials: J
authors.lastname: Montero
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Fardella
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D006977:Hypertension, Renal / Q000097:blood* / Q000235:genetics*; D007438:Introns; D016014:Linear Models; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012083:Renin / Q000097:blood*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D012083:Renin