Gómez-Sánchez E P, Zhou M, Gomez-Sanchez C E
Department of Internal Medicine, University of Missouri-Columbia, USA.
Steroids. 1996 Apr;61(4):184-8. doi: 10.1016/0039-128x(96)00010-4.
Essential hypertensive patients often respond to treatments mitigating mineralocorticoid action, even though circulating levels of these steroids are within normal ranges. In addition to the kidney, mineralocorticoid or Type I receptors are found in the brain and vascular smooth muscle where they mediate effects associated with several forms of experimental hypertension. Studies in which discrete anatomic or functional areas of the brain have been ablated demonstrate that the periventricular areas of the hypothalamus and the central sympathetic and baroreceptor systems are crucial for the development of hypertension in the renoprival, DOCA salt, and Dahl salt-sensitive rat. Intracerebroventricular (i.c.v.) infusion of aldosterone in both rats and dogs at doses that do not raise serum levels above normal produce hypertension. The hypertension produced by systemic mineralocorticoid excess, adrenal regeneration, and i.c.v. or oral administration of glycyrrhetinic acid or carbenoxolone in genetically normotensive rats and by dietary salt in the Dahl salt-sensitive rat is inhibited by the i.c.v. infusion of a mineralocorticoid receptor antagonist or a Na+ channel-selective amiloride analog. Recent data demonstrate the extraadrenal synthesis of steroids in aortic endothelial cells, smooth muscle cells and the brain. The role of the extraadrenal synthesis of steroids raises new avenues for research into the causes of hypertension.
原发性高血压患者常常对减轻盐皮质激素作用的治疗有反应，尽管这些类固醇的循环水平在正常范围内。除了肾脏，盐皮质激素或I型受体还存在于大脑和血管平滑肌中，它们在这些部位介导与几种实验性高血压形式相关的效应。对大脑离散解剖或功能区域进行切除的研究表明，下丘脑的室周区域以及中枢交感神经和压力感受器系统对肾切除、去氧皮质酮盐和 Dahl 盐敏感大鼠的高血压发展至关重要。在大鼠和狗中，以不使血清水平高于正常的剂量进行脑室内（i.c.v.）注射醛固酮会导致高血压。在基因正常血压的大鼠中，由全身性盐皮质激素过量、肾上腺再生以及脑室内或口服甘草次酸或羧苄青霉素引起的高血压，以及在 Dahl 盐敏感大鼠中由饮食中的盐引起的高血压，可通过脑室内注射盐皮质激素受体拮抗剂或Na+通道选择性氨氯地平类似物来抑制。最近的数据表明，类固醇在主动脉内皮细胞、平滑肌细胞和大脑中存在肾上腺外合成。类固醇的肾上腺外合成作用为高血压病因的研究开辟了新的途径。
