Biochemical and genetic characterization of 11 beta-hydroxysteroid dehydrogenase type 2 in low-renin essential hypertensives.
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.
Carvajal
Cristian A
CA
Department of Endocrinology and Metabolism, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Romero
Damián G
DG
Mosso
Lorena M
LM
González
Alexis A
AA
Campino
Carmen
C
Montero
Joaquín
J
Fardella
Carlos E
CE
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
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D012083:Renin