Toriyabe S, Miura Y, Kimura S, Meguro Y, Sugawara T, Noshiro T, Takahashi M, Ohashi H, Sano N, Watanabe H
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai.
Tohoku J Exp Med. 1988 Jun;155(2):129-37. doi: 10.1620/tjem.155.129.
The purpose of this study is to evaluate the plasma Na, K-ATPase inhibitor (NKI) in patients with essential hypertension and to compare the mode of its biochemical actions on the Na, K-ATPase with that of ouabain. Plasma NKI was extracted through a reversed-phase cartridge column and its inhibitory action on hog brain Na, K-ATPase was measured in vitro. Plasma NKI activity was significantly greater in patients with essential hypertension (44 +/- 2.8% (S.E.), n = 28, p less than 0.01) than in normotensive controls (25 +/- 2.4%, n = 21). No significant correlation was demonstrated between the values of plasma NKI and mean arterial pressure in either group. Both plasma NKI and ouabain showed a dose-dependent inhibition on the Na, K-ATPase reaction. An action of ouabain was competitively antagonized by increased concentration of potassium in the reaction mixture, while plasma NKI showed a constant inhibition on the Na, K-ATPase independently of potassium concentrations. The action of plasma NKI was of rapid onset and linear with time, while ouabain showed a delayed onset of the reaction over 30 sec, followed by a progressively increasing inhibition on the enzyme reaction. Finally, the inhibitory action of plasma NKI on Na, K-ATPase was completely abolished in the presence of bovine serum albumin even at the concentration of 500 micrograms/ml in the reaction mixture, which did not have any influence on the actions of ouabain. To sum up, the results showed a markedly different nature of plasma NKI from ouabain in the mode of biochemical actions on the Na, K-ATPase in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在评估原发性高血压患者血浆钠钾 -ATP酶抑制剂(NKI),并比较其对钠钾 -ATP酶的生化作用模式与哇巴因的异同。通过反相柱提取血浆NKI,并在体外测定其对猪脑钠钾 -ATP酶的抑制作用。原发性高血压患者的血浆NKI活性(44±2.8%(标准误),n = 28,p<0.01)显著高于血压正常对照组(25±2.4%,n = 21)。两组中血浆NKI值与平均动脉压之间均未显示出显著相关性。血浆NKI和哇巴因对钠钾 -ATP酶反应均表现出剂量依赖性抑制。反应混合物中钾浓度升高可竞争性拮抗哇巴因的作用,而血浆NKI对钠钾 -ATP酶的抑制作用与钾浓度无关。血浆NKI的作用起效迅速且呈时间线性关系,而哇巴因在30秒后反应延迟开始,随后对酶反应的抑制作用逐渐增强。最后,即使反应混合物中牛血清白蛋白浓度为500微克/毫升,血浆NKI对钠钾 -ATP酶的抑制作用也完全被消除,而这对哇巴因的作用没有任何影响。总之,结果表明,在体外对钠钾 -ATP酶的生化作用模式方面,血浆NKI与哇巴因具有明显不同的性质。(摘要截短至250字)