SODIUM PUMP INHIBITORS IN BLOOD PRESSURE REGULATION

抑制内源性洋地黄样因子(EDLF)的浓度 高血压病患者和实验室的钠泵活性升高 动物，但它们的化学结构，这些海拔的原因， 而它们在高血压发生发展中的作用还有待阐明。 EDLF包括一种哇巴因类化合物(OLC)，它主要来自肾上腺 起源，以及最近发现的一种蟾酥二烯内酯(即 MarinoBufagenin-like化合物或MBG)，从它第一次出现以来就被称为 从蟾酥毒液中分离出来。我们实验室的研究表明，MBG 是一种作用更快、效力更强的大鼠主动脉收缩肌 OLC，在(A)期间刺激MBG的血浆浓度 犬的血浆扩张量，(B)条件呼吸 抑制，增加微型猪的二氧化碳分压，和(C)间隔 人类自愿的低通气量。在本年度内， 给予促肾上腺皮质激素(刺激 肾上腺皮质活动)七天后发现增加 MBG在血浆中的浓度及抑制血管内钠泵活性 大鼠的平滑肌肉。本研究表明，Na，K-ATPase的变化 血管平滑肌的活动不一定能从 红细胞Na，K-ATPase活性的变化。此外，MBG 研究发现，给药对α-1有更大的抑制作用 在血管平滑肌中占主导地位的Na，K-ATPase亚型， 与哇巴因相比，哇巴因有更强的抑制作用 对神经中占优势的Na，K-ATPaseα-3亚型的影响 组织细胞增加基因表达的能力 Na，K-ATPase对钠泵抑制作用的补偿 抑制剂以及对血管张力的影响仍有待阐明 MBG组持续升高的血压。

Concentrations of endogenous digitalis-like factors (EDLF) that inhibit Na pump activity are elevated in hypertensive humans and laboratory animals, but their chemical structures, the causes of these elevations, and their role in the development of hypertension remain to be clarified. EDLF include a ouabain-like compound (OLC) that is primarily of adrenal origin, and a more recently discovered bufodienolide (i.e. a marinobufagenin-like compound or MBG), so-called since it was first isolated in toad venom. Studies in our laboratory have shown that MBG is a more rapidly acting and more potent constrictor of rat aorta than OLC, that plasma concentrations of MBG are stimulated during (a) expansion on plasma volume of dogs, (b) conditioned respiratory suppression that increases pCO2 in micropigs, and (c) intervals of voluntary hypoventilation by humans. During the current year, administration of adrenocorticotrophic hormone (which stimulates adrenocortical activity) for seven days was found to increase concentrations of MBG in plasma and inhibit Na pump activity in vascular smooth muscle of rats. This study showed that changes in Na,K-ATPase activity in vascular smooth muscle cannot necessarily be inferred from changes in erythrocyte Na,K-ATPase activity. In addition, MBG administration was found to have a greater inhibitory effect on alpha-1 isoforms of Na,K-ATPase, which predominate in vascular smooth muscle, than administration of ouabain, while ouabain had a greater inhibitory effect on alpha-3 isoforms of Na,K-ATPase, which predominate in neural tissues The ability of cells to increase genetic expression of Na,K-ATPase to compensate for inhibitory effects of sodium pump inhibitors remains to be clarified, as do the effects on vascular tone and blood pressure of sustained elevations in MBG.