Natriuretic Hormones: Endogenous Na-K-ATPase Inhibitor(s) and Atrial Natriuretic Peptide

Abstract

After the original demonstration of endogenous sodium pump inhibitor(s) in the plasma of acutely fluid volume expanded animals and man, numerous studies have confirmed the presence of ouabainlike factors (OLF) in plasma, urine, cerebrospinal fluid and various tissues. Some of these factors represent well-known endogenous compounds which in vitro reveal inhibition of Na-K-ATPase, displacement of 3H-ouabain and cross-reaction with a digoxin antibody. Small M.W. sodium pump inhibitors (OLF), which may be of hypothalamic origin, were also detected in various animal models of hypertension and in hypertensive patients and may play a role especially in the pathophysiology of volume-dependent hypertension. Our results show that OLF increases basal and vaso-pressin-stimulated intracellular Ca++ release in rat vascular smooth muscle cells in culture and in human platelets similar to the newly discovered endothelin. In plasma and urine natriuretic activities were demonstrated by bioassay whose activity may vary with changes in body sodium balance. We found that they are associated with small peptide(s) with a M.W. of approximately 680 Da. It is, however, not yet clear whether the two biological properties, namely sodium transport inhibition and natriuretic activity, reside in one single compound. A number of circulating Na-K-ATPase inhibitors is certainly not identical with a humoral natriuretic factor. Nevertheless, there is increasing evidence for multiple interactions between OLF and the atrial natriuretic peptide (ANP). Interestingly, recent observations in conscious animals point to a crucial role of a natriuretic factor of non-cardiac origin in the natriuresis of ECFV expansion whose release is also dependent on atrial stretch. These findings represent a new challenge to identify the putative endogenous natriuretic hormone and OLF, respectively, which may act in concert with ANP as regulators of body fluid volume and arterial pressure.