Endogenous Sodium-Transport Inhibitors as Physiological Regulators of the Sodium Pump

  • Garner T. HaupertJr.
Part of the Clinical Physiology Series book series (CLINPHY)

Abstract

since the discovery of endogenous analogues of opium, the endorphins and enkephalins (16, 27), it has been tempting to postulate that parallel situations might obtain for other pharmacologically potent substances from the plant kingdom that exert their effects through specific receptors in animal tissues. Thus the Nat and Ktactivated ATPase (Na+-K+-ATPase) in animal species might have an endogenous analogue to the cardiac glycosides. Several “endogenous factors” that either inhibit active sodium transport, inhibit Na+-K+ATPase activity in vitro, or prevent ouabain binding to the Na+-K+-ATPase have been extracted from amphibian and mammalian sources (for a review, see ref. 12). Such an endogenous sodium-transport inhibitor has been implicated in many important physiological and pathophysiological processes. De Wardener et al. (30) suggested that the natriuresis of intravascular volume expansion was mediated in part by a humoral substance distinct from known regulators of renal hemodynamics and tubular cation transport. Hillyard et al. (15) recognized the ouabainlike effects of such a substance during their attempts to characterize a natriuretic principle extracted from renal tissue of volume-expanded rats. At about the same time Overbeck et al. (21) showed that volume expansion was associated with the elaboration of a heat-stable substance in plasma that inhibited cell membrane sodium transport in vascular muscle, and Haddy and Overbeck (9) postulated that the unknown compound might be responsible for the sequence of physiological events characterizing the development of experimental volume-expanded hypertension in animals. A decrease in sodium-pump activity was documented in uremia (7, 31), and a natriuretic factor was found in the urine of uremic patients with intravascular volume expansion but not in that of nephrotic uremics who demonstrate the physiology of intravascular volume depletion (2). It was hypothesized that this factor might be important in the adaptive response to progressive nephron loss whereby an enhanced fractional excretion of sodium permits maintenance of normal sodium balance in patients with nonnephrotic chronic renal failure (23). It also seems that patients with essential hypertension have an elevated concentration of a circulating pump inhibitor (6, 11, 22), raising the provocative possibility that an abnormality in regulation of Na+-K+-ATPase plays a role in a prevalent human disease.

Keywords

Hydrolysis Vanadate Pyruvate Norepinephrine NADH 

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Copyright information

© American Physiological Society 1987

Authors and Affiliations

  • Garner T. HaupertJr.
    • 1
  1. 1.Renal UnitMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

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