Cortisol metabolism in hypertension
Cortisol metabolism in hypertension
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DOI：
10.1016/j.beem.2006.07.001
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发表时间：
2006-09-01
影响因子：
7.4
通讯作者：
Stewart, Paul M.
中科院分区：
文献类型：
--
作者：
Hammer, Fabian;Stewart, Paul M.
皮质类固醇在血压调节中起关键作用。阿狄森氏病缺乏肾上腺类固醇会导致危及生命的低血压，而库欣综合征的糖皮质激素过量则必然导致高血压。在受体前水平，糖皮质激素的作用由11个β -羟基类固醇脱氢酶（11 β - hsds）调节。11 β - hsid1激活可的松，促进糖皮质激素受体（GR）介导的作用。相比之下，11 β - hsd2在醛固酮靶组织中起关键作用，在那里它催化相反的反应（即皮质醇对可的松的失活），以防止皮质醇激活矿化皮质激素受体（MR）。11 β - hsd2基因的突变导致一种罕见的遗传性高血压，即明显矿化皮质激素过量综合征（AME），其中皮质醇激活MR，导致严重高血压和低钾血症。摄入11 β - hsd2竞争性抑制剂（如甘草和卡贝诺洛酮）会导致类似但较温和的临床表型。流行病学数据表明，HSD11B2基因的多态性变异决定了一般人群的盐敏感性，这是一些患者成人发病高血压的关键易感因素。可能影响血压的糖皮质激素作用和代谢的肾外部位包括血管系统和中枢神经系统。有趣的是，胎儿时期糖皮质激素的增加会促进成年后的高血压，这表明早期编程效应。因此，许多外周组织的代谢和作用可能参与了人类高血压的病理生理。
Corticosteroids are critically involved in blood pressure regulation. Lack of adrenal steroids in Addison's disease causes life-threatening hypotension, whereas glucocorticoid excess in Cushing's syndrome invariably results in high blood pressure. At a pre-receptor level, glucocorticoid action is modulated by 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs). 11 beta-HSID1 activates cortisone to cortisol to facilitate glucocorticoid receptor (GR)-mediated action. By contrast, 11 beta-HSD2 plays a pivotal role in aldosterone target tissues where it catalyses the opposite reaction (i.e. inactivation of cortisol to cortisone) to prevent activation of the mineralocorticoid receptor (MR) by cortisol. Mutations in the 11 beta-HSD2 gene cause a rare form of inherited hypertension, the syndrome of apparent mineralocorticoid excess (AME), in which cortisol activates the MR resulting in severe hypertension and hypokalemia. Ingestion of competitive inhibitors of 11 beta-HSD2 such as liquorice and carbenoxolone result in a similar but milder clinical phenotype. Epidemiological data suggests that polymorphic variability in the HSD11B2 gene determines salt sensitivity in the general population, which is a key predisposing factor to adult onset hypertension in some patients. Extrarenal sites of glucocorticoid action and metabolism that might impact on blood pressure include the vasculature and the central nervous system. Intriguingly, increased exposure to glucocorticoids during fetal life promotes high blood pressure in adulthood suggesting an early programming effect. Thus, metabolism and action in many peripheral tissues might contribute to the pathophysiology of human hypertension.