Parallel observations in gut microbiology coupled with screening of endogenous steroids as inhibitors of 11β-HSD2 have implicated particular gut bacteria in essential hypertension through the production of glycerrhetinic acid-like factors (GALFs).
As 50% of patients with essential hypertension are insulin resistant and hyperinsulinemic, we hypothesized that insulin downregulates the 11beta-HSD2 activity.
Whereas mutations or inhibition of 11βHSD2 by licorice have been clearly shown to produce a congenital or acquired syndrome of mineralocorticoid excess, the questions remaining are the extent to which subtle abnormalities in MR/11βHSD2 mechanisms may contribute to essential hypertension.
Inhibition of 11beta-HSD2 explains the mineralocorticoid excess state seen following liquorice ingestion and more subtle defects in enzyme expression might be involved in the pathogenesis of 'essential' hypertension.
HSD11B2 does not have a strong influence on the development of essential hypertension in Black people, but weaker effects on blood pressure cannot beruled out.
To address this, the coding sequences of the 11BHSD2 gene was screened for mutations in 20 patients with primary hypertension with single strand conformation polymorphism and direct DNA sequencing techniques.
Hypertension with no other characteristic signs of AME was found in the heterozygous father of a child with AME, and we described a girl with a homozygous gene mutation resulting in only a slightly reduced 11 beta HSD2 activity causing 'essential' hypertension.
In normals or in subjects with essential hypertension, sensitivity of blood pressure to salt loading is correlated with activity of renal 11-HSD2, as measured by an increase in the ratio of urinary free cortisol/urinary free cortisone (UFF/UFE), and also correlated with length of a CA repeat polymorphism in the first intron of HSD11B2.
Finally, while some studies demonstrate impaired 11beta-HSD activity in broader populations of patients with hypertension, further studies are required to clarify the role of 11beta-HSD2 in 'essential' hypertension.
Hypertensive populations should be screened to identify the prevalence of milder defects in 11beta-HSD2 in patients currently labeled as having "essential" hypertension.
These data indicate the presence of a polymorphic marker in exon 3 of the HSD11B2 gene; this marker is associated with end-stage renal disease but not with essential hypertension in humans.