Role of renal Na⁺,K⁺-ATPase in the regulation of sodium excretion under normal conditions and in acute congestive heart failure

Background. Cardiac glycosides have traditionally been used as inotropic agents in the treatment of congestive heart failure (CHF). The renal actions of cardiac glycosides independent of inotropic effects are not characterized. The presence of endogenous digitalis-like factors (EDLFs) with characteristic Na⁺,K⁺-ATPase activity has been postulated in volume-expanded states such as CHF, and recent studies have demonstrated that at least one EDLF shares structural homology with ouabain. This study was undertaken to evaluate the renal actions of ouabain in normal dogs and those with CHF. Methods and Results. After surgical preparation, normal dogs (n=6) and dogs in pacing-induced CHF (n=6) received intrarenal ouabain in sequential doses of 0.167 μg/kg/min, 0.334 μg/kg/min, and 0.668 μg/kg/min. Hemodynamics and renal function were evaluated during the infusion. There was no change in heart rate or mean arterial pressure during the infusion compared with baseline in both groups. Sodium excretion and urine volume significantly increased in both groups. Plasma renin activity, activated by the onset of pacing in the CHF group, was inhibited by the administration of intrarenal ouabain in this group only. Conclusions. These studies demonstrate that ouabain has diuretic and natriuretic actions independent of cardiac hemodynamics that are preserved in CHF. Furthermore, intrarenal ouabain suppresses activation of renin in CHF.