DIRECT RENAL ACTION OF SOME DIGITALIS STEROIDS * By JAMES C. STRICKLER t AND RICHARD H. KESSLER: WITH THE TECHNICAL

Some digitalis steroids alter the activity of cardiac muscle. Applying the bioassay technique in cats and frogs, Chen and co-workers (1-4) screened many structural variants of the clinically useful digitalis compounds for cardiac action. They were able to distinguish the active from the inactive steroids by their chemical structure. The major features common to those compounds ex-hibiting cardiac activity include a cyclopentano-phenanthrene nucleus with a hydroxyl substituent at the C-14 position and an unsaturated, 5 or 6 membered lactone ring in /8 orientation at C-17. Those compounds in which the lactone ring was either saturated or in a orientation lacked cardiac activity. Synthesis of active digitalis steroids without the C-14 hydroxyl has not been accom-plished to date and, therefore, the role of this constituent is unknown. In addition to their familiar actions on cardiac muscle, these steroids affect cation movement in several tissues (5-15). Inhibition of the active ion transport mechanism is the common effect produced. Glynn (9), Schatzmann (5), and others (6-8), for example, have shown that the cardiac active steroids, in a concentration of about 1 Itg/ml, depress potassium influx and sodium efflux in the human red cell. Depending upon the cell type, passive diffusion fluxes may or may not be inhibited. Glynn also studied certain molecular requirements for this inhibitory effect and found them identical to those necessary for cardiac activity. He concluded that the configuration at C-17 of the steroid nucleus is important and that saturation of the lactone ring greatly reduces activity. The first data suggesting that digitalis steroids might directly affect renal electrolyte transpor