Partial purification and properties of a plasma ouabain-like inhibitor of Na+, K+-ATPase in patients with essential hypertension.

Abstract

Plasma levels of an ouabain-like inhibitor of Na+,K+-ATPase were higher in patients with essential hypertension compared with normal levels. The ouabain-like inhibitor was correlated significantly with blood pressure and was increased by a high-salt diet. The substance was partially purified by high performance liquid chromatography which revealed lipid-like properties, but the elution time was different from that of free unsaturated fatty acid on silica-gel high performance liquid chromatography. Its molecular weight was 600 or less, as estimated by high performance liquid chromatography with an HSG-15H column. The ouabain-like substance inhibited Na+, K+-ATPase in competition with KCl and showed positive ouabain-like immunoreactivity, whereas lysophosphatidylcholine was a non-competitive inhibitor. The ouabain-like substance was unstable at room temperature and decomposed to smaller molecular compounds which did not inhibit Na+, K+-ATPase. The inhibitory fraction gave a positive thiobarbituric acid reaction test. The mobility of the ouabain-like inhibitor on silica-gel thin-layer chromatography was different from that of prostaglandins and arachidonic acid. These results indicate that the plasma ouabain-like inhibitor of patients with essential hypertension is a lipid which is different from free fatty acid or lysophosphatidylcholine, and may be an unstable peroxide.