Studies on the Sites of Action of Ethacrynic Acid and Furosemide During Angiotensin Infusion

¹ Isotopic Department and Metabolic Unit and Department of Medicine, János Hospital, XII. Diósárok ut 1., Budapest, Hungary.

Effects of ethacrynic acid and furosemide were studied on specific renal functions with special reference to diluting operation during angiotensin infusion in maximal sustained water diuresis in eight healthy subjects. Effects of ethacrynic acid without angiotensin were also studied.

The consistent increase in free water formation induced by furosemide during angiotensin infusion suggested a proximal tubular action. Increasing free water clearance was demonstrated in some subjects also during ethacrynic acid diuresis induced under angiotensin effect. In other subjects, free water excretion decreased even during angiotensin infusion. Without angiotensin, free water clearance was consistently diminished by ethacrynic acid.

It was concluded that (1) in addition to the major Henle's loop effect, ethacrynic acid also has a proximal tubular action, probably playing some role in the reversal of the angiotensin-induced antidiuresis and antinatriuresis; (2) furosemide has a greater inhibitory effect on sodium reabsorption in the proximal tubule and a weaker action in the ascending limb of the loop of Henle than does ethacrynic acid.

Note:

We are greatly indebted to Drs. W.H. Wilkinson (West Point, Pa.) and Andrial Milorad (Zurich) and to Merck, Sharp and Dohme as well as to Dr. Wellner (Frankfort am Main) and to the firm Hoechst, for the generous supplies of ethacrynic acid (Edecrin-Lyovac) and furosemide (Lasix), respectively.

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