The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of human hypertension thought to result from a deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD).
The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of human hypertension thought to result from a deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD).
Furthermore, in the rat, an association between placental 11 beta HSD activity and the subsequent development of hypertension in the offspring has been reported.
Mutations in the HSD11K (HSD11B2) gene encoding this isozyme cause a genetic form of hypertension, the syndrome of apparent mineralocorticoid excess (AME).
The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is defective.
Mutations generating inactive enzymes have been described in the HSD11B2 gene in the congenital syndrome of apparent mineralocorticoid excess (AME)--a low renin form of hypertension.
Mutations of the gene encoding 11beta-HSD-2 are responsible for the syndrome of apparent mineralocorticoid excess, in which cortisol illicitly occupies mineralocorticoid receptors, causing hypertension and hypokalaemia.
AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11beta-HSD2 gene; classification into distinct subtypes is inappropriate.
Statistical analyses using the affected sib-pair method did not show significant linkage between the 11beta-HSD2 microsatellite marker and hypertension.
In congenital 11beta-HSD deficiency and after administration of 11beta-HSD inhibitors, suppression of 11beta-HSD2 activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension.
These results reveal that cholic acid is able to induce hypertension and provide evidence that cholic acid inhibits the transcription of both 11beta-HSD2 and CYP11B2 in vasculature, leading to lower aldosterone and higher corticosterone production in vessels and increased vasoconstrictor responses to norepinephrine.
Thus, depending on the degree of loss of enzyme activity, 11 beta HSD2 mutations can cause a spectrum of phenotypes ranging from severe, life-threatening hypertension in infancy to a milder form of the disease in adults.
In the development of diabetes-induced hypertension, the effect of spironolactone on mean systolic blood pressure may be associated with the mineralocorticoid effects of corticosterone on renal MR, as well as an alteration of renal 11beta-HSD2 activity and its mRNA expression in insulin-dependent diabetic rats.
Because the hypertension associated with AME is of the salt-sensitive type, it seemed possible that decreases in 11-HSD2 activity might be associated with salt sensitivity.
Because polymorphisms in HSD11B2 have been associated with hypertension and salt sensitivity, we characterized the human VPATPD gene.It spans 19 kb and consists of 8 exons.
Mutations in the HSD11B2 gene encoding the kidney (11-HSD2) isozyme of 11beta-hydroxysteroid dehydrogenase cause the syndrome of apparent mineralocorticoid excess, a form of salt-sensitive hypertension.