ENDOGENOUS INHIBITORS OF THE NA,K PUMP

Evidence for a 'third factor' in the regulation of urinary sodium excr etion has directed a search for a natriuretic agent which functions by inhibition of Na,K-ATPase. Such an agent may also be involved in the genesis of hypertension and provide an important pathophysiological li nk between increased sodium intake, reduced renal sodium excretory cap acity and hypertension. Numerous lines of evidence have been developed , all supporting the possibility that third factor sodium pump inhibit ion may take place through the cardiac glycoside-binding site of the s odium pump. Inhibition of the sodium pump may contribute to renal mech anisms of sodium balance. Generalization of this inhibition to vascula r tissue and to the neural tissue regulating vascular contraction may elevate blood pressure (and increase natriuresis) by increasing contra ction. In spite of 30 years of effort, no convincing substance has bee n successfully identified as both a cardiac glycoside-like inhibitor o f the sodium pump and an endogenous substance. However, recent work ha s led to the emergence and investigation of a number of interesting ca ndidates. This review will survey the historical background of endogen ous sodium pump inhibitors, examine some of the problems and requireme nts which must be overcome in their identification, analyze evidence o btained recently concerning a number of candidate compounds and identi fy problems which remain to be addressed in this field.