Hatakeyama H, Inaba S, Taniguchi N, Miyamori I
Third Department of Internal Medicine, Fukui Medical University, Fukui, Japan.
Hypertension. 2000 Nov;36(5):862-5. doi: 10.1161/01.hyp.36.5.862.
Hypertension is a prominent feature of patients with Cushing's disease and ectopic adrenocorticotropic hormone (ACTH) syndrome, who have elevated ACTH levels. Chronic administration of ACTH (1-24) also raises blood pressure in humans. This effect has been postulated to be due to ACTH-induced increases in cortisol secretion in the adrenal gland. It is well known that cortisol increases vascular tone by potentiating the vasoconstrictor action of a number of pressor hormones. In the present study, we show direct evidence that human aortic endothelial cells possess the ACTH receptor. 11beta-Dehydrogenation, converting cortisol to its inactive metabolite, cortisone, mediated by vascular 11beta-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-dependently decreased the gene expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 2 in these cells, and the decrease was partially abolished by a selective ACTH receptor antagonist. This may indicate that ACTH potentiates the action of cortisol through its direct effect on the vasculature. Therefore, the present study provides important information for understanding the mechanism of ACTH-induced hypertension.
高血压是库欣病和异位促肾上腺皮质激素（ACTH）综合征患者的一个显著特征，这些患者的ACTH水平升高。长期给予ACTH（1 - 24）也会使人类血压升高。据推测，这种作用是由于ACTH诱导肾上腺皮质醇分泌增加所致。众所周知，皮质醇通过增强多种升压激素的血管收缩作用来增加血管张力。在本研究中，我们提供了直接证据，表明人主动脉内皮细胞拥有ACTH受体。由血管2型11β - 羟基类固醇脱氢酶介导的11β - 脱氢作用，将皮质醇转化为其无活性代谢产物可的松，对于控制血管张力至关重要，而该酶活性降低可能与高血压的发病机制有关。我们发现，ACTH（1 - 24）在这些细胞中剂量依赖性地降低2型11β - 羟基类固醇脱氢酶的基因表达和酶活性，并且这种降低被一种选择性ACTH受体拮抗剂部分消除。这可能表明ACTH通过其对血管系统的直接作用增强了皮质醇的作用。因此，本研究为理解ACTH诱导的高血压机制提供了重要信息。
