Endogenous renal 11 beta-hydroxysteroid dehydrogenase inhibitory factors in patients with low-renin essential hypertension.
11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and is important in blood pressure control. The excretion of renal 11 beta-HSD (ie, NAD(+)-dependent isoform) is thought to protect renal mineralocorticoid receptors from cortisol. To examine whether endogenous renal 11 beta-HSD inhibitory factor(s) may be involved in the pathophysiology of hypertension, we studied the urinary excretion of such inhibitors in 30 patients with low-renin essential hypertension and 20 normotensive control subjects. The effect of sodium restriction on the urinary excretion of the inhibitors wa also evaluated in six normotensive control subjects. Urine was extracted with Sep-Pak cartridges and high-performance liquid chromatography. Endogenous renal 11 beta-HSD inhibitors were measured by the inhibition of 11 beta-HSD bioactivity in microsomes from the human kidney. The urinary excretion of the inhibitors was significantly increased in patients with low-renin essential hypertension (1280 +/- 88 nmol/d, mean +/- SEM) compared with normotensive control subjects (704 +/- 56 nmol/d) (P < .05). Ratios of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone did not differ significantly. Sodium restriction reduced the urinary excretion of the endogenous renal 11 beta-HSD inhibitors but did not affect the ratio of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone. Endogenous renal 11 beta-HSD inhibitory factors may contribute to the pathogenesis of low-renin essential hypertension by modulating the activity of 11 beta-HSD. Sodium intake may directly or indirectly regulate the inhibitory factors.
Takeda
Y
Y
Second Department of Internal Medicine, School of Medicine, Kanazawa, Japan.
Miyamori
I
I
Iki
K
K
Inaba
S
S
Furukawa
K
K
Hatakeyama
H
H
Yoneda
T
T
Takeda
R
R
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004039:Diet, Sodium-Restricted; D004791:Enzyme Inhibitors / Q000032:analysis / Q000652:urine*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D007668:Kidney / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood / Q000652:urine; D012016:Reference Values; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000652:urine
D004791:Enzyme Inhibitors; D000450:Aldosterone; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D012083:Renin; D011188:Potassium; D006854:Hydrocortisone