Na-K-ATPase inhibitor dissociated from hypertension-associated plasma protein

It has been demonstrated that human plasma contains a low molecular weight sodium-potassium-stimulated adenosine triphosphatase (Na-K-ATPase) inhibito r, which can be dissociated from a circulating protein:with a molecular wei ght of approximately 12,000 daltons. The dissociated factor was found to ha ve a molecular weight <500 daltons, and shared many characteristics with ou abain. Similar to ouabain, this factor was found to be a potent inhibitor o f both the Na-K-ATPase and potassium-stimulated para-nitrophenyl phosphatas e (K-pNPPase) enzyme systems, and to bind to both high- and low-affinity bi nding sites on Na-K-ATPase, but unlike ouabain did not crossreact with digo xin antibody. The factor was further separated by HPLC and electrochemical detection into two active compounds (p-NKAI-1 and p-NKAI-2). P-NKAI-1 was d emonstrated on mass spectroscopy to have a molecular weight of 408 daltons. In a vasoconstrictor assay employing rabbit femoral artery segments, this compound was a direct vasoconstrictor and potentiated the vasoconstriction produced by norepinephrine. It behaved similarly to ouabain in counteractin g the relaxing effect on rabbit femoral artery of increasing potassium conc entrations in the tissue bath. (C) 1999 American Journal of Hypertension, L td.