Functional adrenocorticotropic hormone receptor in cultured human vascularendothelial cells - Possible role in control of blood pressure

Hypertension is a prominent feature of patients with Gushing's disease and ectopic adrenocorticotropic hormone (ACTH) syndrome, who have elevated ACTH levels. Chronic administration of ACTH (1-24) also raises blood pressure i n humans. This effect has been postulated to be due to AGTH-induced increas es in cortisol secretion in the adrenal gland. It is well known that cortis ol increases vascular tone by potentiating the vasoconstrictor action of a number of presser hormones. In the present study, we show direct evidence t hat human aortic endothelial cells possess the ACTH receptor. Il P-Dehydrog enation, converting cortisol to its inactive metabolite, cortisone, mediate d by vascular 11 beta -hydroxysteroid dehydrogenase type 2 is essential for the control of vascular tone, and the reduced activity may be relevant to the pathogenesis of hypertension. We found that ACTH (1-24) dose-dependentl y decreased the gene expression and enzyme activity of 11 beta -hydroxyster oid dehydrogenase type 2 in these cells, and the decrease was partially abo lished by a selective ACTH receptor antagonist. This may indicate that ACTH potentiates the action of cortisol through its direct effect on the vascul ature. Therefore, the present study provides important information for unde rstanding the mechanism of ACTH-induced hypertension.