A Plasma Inhibitor of Sodium and Potassium Activated Adenosine Triphosphatase in Patients with Essential Hypertension

TORIYABE, S., MIURA, Y., KIMURA, S., MEGURO, Y., SUGAWARA, T., NOSHIRO, T., TAKAHASHI, M., OHASHI, H., SANO, N., WATANABE, H. and YOSHINAGA, K. A Plasma Inhibitor of Sodium and Potassium Activated Adenosine Triphosphatase in Patients with Essential Hypertension. Tohoku J. exp. Med., 1988, 155 (2), 129-137 - 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<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 30sec, 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 500μg/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. This study may also raise a question whether plasma free NKI, supposedly an active from of NKI, is actually working as a physiological regulator in vivo. It seems thus premature to assume it as a pathogenic factor in essential hypertension.