Doris P A
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Miner Electrolyte Metab. 1996;22(5-6):303-10.
Evidence for a 'third factor' in the regulation of urinary sodium excretion has directed a search for a natriuretic agent which functions by inhibition of Na,K-ATPase. Such an agent may also be involved in the genesis of hypertension and provide an important pathophysiological link between increased sodium intake, reduced renal sodium excretory capacity and hypertension. Numerous lines of evidence have been developed, all supporting the possibility that third factor sodium pump inhibition may take place through the cardiac glycoside-binding site of the sodium pump. Inhibition of the sodium pump may contribute to renal mechanisms of sodium balance. Generalization of this inhibition to vascular tissue and to the neural tissue regulating vascular contraction may elevate blood pressure (and increase natriuresis) by increasing contraction. In spite of 30 years of effort, no convincing substance has been successfully identified as both a cardiac glycoside-like inhibitor of the sodium pump and an endogenous substance. However, recent work has led to the emergence and investigation of a number of interesting candidates. This review will survey the historical background of endogenous sodium pump inhibitors, examine some of the problems and requirements which must be overcome in their identification, analyze evidence obtained recently concerning a number of candidate compounds and identify problems which remain to be addressed in this field.
关于尿钠排泄调节中“第三因子”的证据，引发了对一种通过抑制钠钾ATP酶发挥作用的利钠剂的探寻。这种物质可能也参与了高血压的发病过程，并在钠摄入量增加、肾钠排泄能力降低与高血压之间提供了重要的病理生理联系。现已积累了大量证据，均支持第三因子对钠泵的抑制作用可能通过钠泵的强心苷结合位点发生这一可能性。钠泵的抑制作用可能有助于维持肾脏的钠平衡机制。这种抑制作用扩展至血管组织以及调节血管收缩的神经组织，可能会通过增强收缩作用来升高血压（并增加利钠作用）。尽管经过30年的努力，尚未成功鉴定出一种既具有类似强心苷对钠泵的抑制作用又属于内源性的物质。然而，近期的研究已促使一些有趣的候选物质出现并得到研究。本综述将概述内源性钠泵抑制剂的历史背景，探讨在其鉴定过程中必须克服的一些问题和要求，分析近期获得的有关一些候选化合物的证据，并明确该领域中仍有待解决的问题。
