DIRECT RENAL ACTION OF SOME DIGITALIS STEROIDS*

Abstract

This study amplifies previous observations that digitalis steroids act directly on the kidney to increase water and electrolyte excretion. The mechanism of this action may be inferred from observations of Glynn and others who demonstrated that certain of these compounds inhibit ion movements across red cell membranes. In the present work some cardiac active glycosides and derivatives were infused into one renal artery of saline loaded dogs. Those compounds known to have cardiac toxicity or to affect ion fluxes increased Na+ and water excretion. These effects could not be attributed to alterations in renal hemodynamics. At times Na+ excretion exceeded 35% of the filtered load, suggesting profound inhibition of sodium re-absorption in the proximal tubule. Several cardiac inactive compounds did not produce these changes despite a marked increase in dosage. As also noted by Glynn, features common to the active compounds include an unsaturated 5 or 6 membered lactone ring and a specific steric relationship of the lactone ring to the C-17 carbon of the steroid nucleus. Our results demonstrate that only the cardiac active compounds increase urine flow and electrolyte excretion when infused into a renal artery.