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(Hypertension. 1999;33:1179-1184.)
© 1999 American Heart Association, Inc.

Scientific Contributions

11ß-Hydroxysteroid Dehydrogenase in Cultured Human Vascular Cells

Possible Role in the Development of Hypertension

Haruhiko Hatakeyama; Satoru Inaba; Isamu Miyamori

From the Third Department of Internal Medicine, Fukui Medical University (Japan).

Correspondence to Haruhiko Hatakeyama, MD, Third Department of Internal Medicine, Fukui Medical University, 23-1 Matsuoka-cho, Fukui 910-1141, Japan.

Abstract—11ß-Hydroxysteroid dehydrogenases (11ß-HSD) interconvert cortisol, the physiological glucocorticoid, and its inactive metabolite cortisone in humans. The diminished dehydrogenase activity (cortisol to cortisone) has been demonstrated in patients with essential hypertension and in resistance vessels of genetically hypertensive rats. 11ß-Hydroxysteroid dehydrogenase type 2 (11ß-HSD2) catalyzes only 11ß-dehydrogenation. However, a functional relationship between diminished vascular 11ß-HSD2 activity and elevated blood pressure has been unclear. In this study we showed the expression and enzyme activity of 11ß-HSD2 and 11ß-HSD type 1 (which is mainly oxoreductase, converting cortisone to cortisol) in human vascular smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by upregulating the receptors of pressor hormones such as angiotensin II. We found that physiological concentrations of cortisol-induced increase in angiotensin II binding were significantly enhanced by the inhibition of 11ß-HSD2 activity with an antisense DNA complementary to 11ß-HSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired 11ß-HSD2 activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11ß-HSD deficiency and after administration of 11ß-HSD inhibitors, suppression of 11ß-HSD2 activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. In the present study we provide evidence for a mechanism that could link impaired vascular 11ß-HSD2 activity, increased vascular tone, and elevated blood pressure without invoking renal sodium retention.

Key Words: 11ß-hydroxysteroid dehydrogenase • receptors, angiotensin II • cortisol • vascular tone • hypertension, essential

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