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11beta-hydroxysteroid dehydrogenase in cultured human vascular cells. Possible role in the development of hypertension.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hatakeyama, Haruhiko Inaba, Shinji Miyamori, Isamu |
| Copyright Year | 1999 |
| Abstract | 11beta-Hydroxysteroid dehydrogenases (11beta-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. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) catalyzes only 11beta-dehydrogenation. However, a functional relationship between diminished vascular 11beta-HSD2 activity and elevated blood pressure has been unclear. In this study we showed the expression and enzyme activity of 11beta-HSD2 and 11beta-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 11beta-HSD2 activity with an antisense DNA complementary to 11beta-HSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired 11beta-HSD2 activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. 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. In the present study we provide evidence for a mechanism that could link impaired vascular 11beta-HSD2 activity, increased vascular tone, and elevated blood pressure without invoking renal sodium retention. |
| Starting Page | 1 |
| Ending Page | 4 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://hyper.ahajournals.org/content/hypertensionaha/33/5/1179.full.pdf |
| PubMed reference number | 10334808v1 |
| Volume Number | 33 |
| Issue Number | 5 |
| Journal | Hypertension |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 11-beta-Hydroxysteroid Dehydrogenase Type 2 17-Hydroxysteroid Dehydrogenase Deficiency Aldosterone Angiotensin II Angiotensins Blood Vessel Cortisone Glucocorticoids Hydrocortisone Hydroxysteroid Dehydrogenases Hydroxysteroids Hyperaldosteronism Hypernatremia Hypertensive disease Ketoglutarate Dehydrogenase Complex Mineralocorticoid Receptor Antagonists Mineralocorticoids Muscle, Smooth, Vascular Myocytes, Smooth Muscle Oxidoreductase Patients Physical Inactivity Pulmonary Hypertension Renal Tissue Smooth muscle (tissue) Sodium Sodium, Dietary Spondyloepiphyseal dysplasia, Omani type antisense therapy enzyme activity |
| Content Type | Text |
| Resource Type | Article |
