Hamlyn J M, Hamilton B P, Manunta P
Department of Physiology, School of Medicine, University of Maryland, Baltimore 21201, USA.
J Hypertens. 1996 Feb;14(2):151-67. doi: 10.1097/00004872-199602000-00002.
To assess possible relationships between endogenous ouabain, sodium balance and blood pressure.
This review concerns the structure of endogenous ouabain, circulating levels of this steroid in various disorders of fluid and electrolyte balance, recent evidence for the association of endogenous ouabain with human hypertension, the influence of sodium and volume factors on ouabain-induced hypertension, and possible mechanisms for the hypertensinogenic activity of ouabain.
The human circulation contains a closely related isomer of ouabain of putative adrenocortical origin. Elevated circulating levels of this 'endogenous ouabain' are common but not universal in physiologic and pathologic states associated with positive sodium balance or high blood pressure, or both. In the absence of adrenal hyperfunction, elevating circulating levels of endogenous ouabain appear to be secondary to impaired renal clearance. Prolonged elevation of circulating ouabain in the rat induces sustained hypertension. This model exhibits normal plasma renin activity, increased levels of ouabain in the hypothalamus, pituitary, and kidney, and responds to angiotensin converting enzyme inhibitor. In rats with normal kidney function, ouabain-induced hypertension is primarily sodium-insensitive although maneuvers that hinder renal sodium excretion augment the pressor effect of this steroid. Prolonged administration of ouabain into the brain ventricles augments sympathetic nervous system activity and induces sustained hypertension. These observations lead us to propose the following hypothesis. Among Caucasian patients with essential hypertension, a large fraction have elevated circulating levels of endogenous ouabain, possibly caused by an inherited or acquired renal defect in clearance of this steroid. In these patients, and in rats with ouabain-induced hypertension, increased local generation of, or increased target organ sensitivity to, angiotensin II, or both, may contribute critically to heightened vasoconstriction and a sustained increase in blood pressure. Investigations of the efferent pressor mechanisms and the renal handling of endogenous ouabain are novel approaches to the etiology and therapy of several common cardiovascular disorders.
评估内源性哇巴因、钠平衡与血压之间可能存在的关系。
本综述涉及内源性哇巴因的结构、在各种体液和电解质平衡紊乱中该类固醇的循环水平、内源性哇巴因与人类高血压关联的最新证据、钠和容量因素对哇巴因诱导的高血压的影响，以及哇巴因致高血压活性的可能机制。
人体循环中含有一种假定源自肾上腺皮质的与哇巴因密切相关的异构体。在与正钠平衡或高血压或两者相关的生理和病理状态下，这种“内源性哇巴因”的循环水平升高很常见，但并非普遍现象。在无肾上腺功能亢进的情况下，内源性哇巴因循环水平升高似乎继发于肾脏清除功能受损。大鼠循环中哇巴因的长期升高会诱发持续性高血压。该模型表现出正常的血浆肾素活性、下丘脑、垂体和肾脏中哇巴因水平升高，并且对血管紧张素转换酶抑制剂有反应。在肾功能正常的大鼠中，哇巴因诱导的高血压主要对钠不敏感，尽管阻碍肾脏排钠的操作会增强这种类固醇的升压作用。向脑室长期注射哇巴因会增强交感神经系统活性并诱发持续性高血压。这些观察结果使我们提出以下假设。在患有原发性高血压的白种人患者中，很大一部分人的内源性哇巴因循环水平升高，这可能是由于该类固醇清除的遗传性或获得性肾脏缺陷所致。在这些患者以及哇巴因诱导的高血压大鼠中，血管紧张素II的局部生成增加或靶器官对其敏感性增加，或两者兼而有之，可能对血管收缩增强和血压持续升高起关键作用。对内源性哇巴因传出升压机制和肾脏处理的研究是几种常见心血管疾病病因学和治疗的新方法。
