ATTENUATION OF AZOSEMIDE ACTION IN THE LOOP OF HENLE OF RAT-KIDNEY BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS

The purpose of the present study, which was performed in anaesthetized rats, was to clarify whether the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and meclofenamate interact with the diuretic action of the new loop diuretic azosemide (Luret(R), CAS-27589-33-9). Since azosemide's diuretic action shows a lower onset and a more prolonged duration as compared to classical loop diuretics it was also tested whether azosemide's tubular action is mediated by an active metabolite. The results demonstrate that azosemide, when infused directly into the lumen of superficial loops of Henle, dose-dependently diminished the loops sodium and chloride reabsorption. A half-maximum effect was observed at an azosemide concentration of 3 x 10(-6) mol/l. These results clearly prove that the diuretic effect of azosemide is exerted by the drug itself and does not require metabolism to an active metabolite. Luminal application of the drug also dose-dependently increased early distal sodium and chloride concentrations, indicating that the drug's tubular action is located in the thick ascending limb of Henle's loop. Indomethacin and meclofenamate blunted the diuretic, natriuretic and chloruretic response to azosemide, and microperfusion experiments on single loops of Henle revealed an attenuation by NSAIDs of azosemide's inhibitory action on the loops sodium and chloride reabsorption. The quantitative extent of this interaction was nearly identical to that observed previously for the NSAID-furosemide interaction.