Dehydroepiandrosterone prevents dexamethasone-induced hypertension in rats

Abstract

Dehydroepiandrosterone (DHEA) is an endogenous steroid having a wide variety of biological and biochemical effects. In the present study, we have examined the role of DHEA on various rodent models of experimental hypertension. Sprague-Dawley rats were given subcutaneous injections of 1.5 mg dexamethasone every alternate day, resulting in an increase in systolic blood pressure within 1 wk. Interestingly, administration of a pharmacological dose of 1.5, 3, or 7.5 mg DHEA along with dexamethasone prevented dexamethasone-induced hypertension in a dose-dependent manner. DHEA had no effect on the hypertension induced by deoxycorticosterone acetate (DOCA)-salt administration using uninephrectomized rats or on the genetic model of spontaneously hypertensive rats. Dexamethasone administration resulted in a significant weight loss in rats, which was not prevented by simultaneous administration of DHEA. These results indicate that dexamethasone-mediated weight loss may involve mechanisms separate from its hypertensive action. Dexamethasone treatment resulted in a significant decrease in food consumption that was not reversed by DHEA. It is concluded that DHEA at doses above physiological levels when given subcutaneously has no effect on DOCA-salt or a genetic model of hypertension but has a beneficial effect on dexamethasone-induced hypertension.

Non-Hypertensive Deoxycorticosterone-Salt Treatment Accelerates Atherosclerosis Progression in Watanabe Heritable Hyperlipidemic Rabbit

“…For instance DOCA binds to both type-I (mineralocorticoid) and type-II (glucocorticoid) re ceptors [59] and we cannot rule out that part of the weight loss, as a part of the effect on atherosclerotic lesions observed in DOCA-salt treated rabbits, might be me diated via the activation of glucocorticoid receptors. In deed, dexamethasone treatment produced a significant weight loss resulting from a major decrease in food con sumption [60,61]. Another possibility is that weight loss could be caused by potassium supplementation.…”

Hormonersatz mittels DHEA plus Glukokortikoide in der Therapie von Patienten mit chronisch entzündlichen Erkrankungen

“…Several studies pointed out that DHEA has anti-glucocorticoid activities with respect to lymphocyte proliferation (12), thymic involvement (74), immune function in mice after thermal injury (4), macrophage activity (87), induction of liver enzymes (135), neurotoxic effects of dexamethasone (55), and glucocorticoid-induced hypertension (105). Currently, the mode of anti-glucocorticoid action is not exactly known but reduction of glucocorticoid receptors by DHEA may be a possible mechanism (14, 43).…”

DHEA and Immune Function: Activities and Mechanism of Action

“…81 Dehydroepi androsterone is not working, however, by directly competing for dexamethasone binding to the GC receptor. 82 Dehydroepiandrosterone has also been reported to affect signal transduction pathways and the presence of certain cellular enzymes in the oppo-site manner of GCs. 37 One such enzyme is glucose-6phosphate dehydrogenase (G6PD), a constituent of the hexose monophosphate shunt.…”