Functional adrenocorticotropic hormone receptor in cultured human vascular endothelial cells - Possible role in control of blood pressure
Functional adrenocorticotropic hormone receptor in cultured human vascular endothelial cells - Possible role in control of blood pressure
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DOI：
10.1161/01.hyp.36.5.862
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发表时间：
2000-11-01
期刊：
影响因子：
8.3
通讯作者：
Miyamori, I
中科院分区：
文献类型：
--
作者：
Hatakeyama, H;Inaba, S;Miyamori, I
高血压是库欣病和异位促肾上腺皮质激素（ACTH）综合征患者的显著特征，其ACTH水平升高。长期服用ACTH（1-24）也会升高人体血压。这种效应被认为是由于ACTH诱导的肾上腺皮质醇分泌增加。众所周知，皮质醇通过增强许多加压激素的血管收缩作用来增加血管张力。在本研究中，我们显示直接的证据表明，人主动脉内皮细胞具有ACTH受体。血管11 β-羟基类固醇脱氢酶2型介导的β-脱氢作用，将皮质醇转化为无活性代谢产物可的松，是控制血管张力所必需的，活性降低可能与高血压的发病机制有关。我们发现ACTH（1-24）剂量依赖性地降低这些细胞中11 β-羟类固醇脱氢酶2型的基因表达和酶活性，并且这种降低被选择性ACTH受体拮抗剂部分消除。这可能表明ACTH通过其对脉管系统的直接作用而增强皮质醇的作用。本研究为进一步了解ACTH致高血压的机制提供了重要信息。
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 presser hormones. In the present study, we show direct evidence that human aortic endothelial cells possess the ACTH receptor. Il P-Dehydrogenation, converting cortisol to its inactive metabolite, cortisone, mediated 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-dependently decreased the gene expression and enzyme activity of 11 beta -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.