FUROSEMIDE AND HYDROCHLOROTHIAZIDE DO NOT HAVE A COMMON MODE OF ACTION

¹ Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota

The purpose of this study was to find out whether hydrochlorothiazide (HCTZ) and the more efficacious diuretic, furosemide, have a common mode of action (i.e., react with the same renal receptors) or have separate and distinctive modes of action. This was accomplished through use of Ex 4877, a competitive antagonist of the diuretic action of HCTZ. The antagonist did not modify diuretic response to furosemide in anesthetized dogs even though response to HCTZ was completely blocked. The possibility that furosemide had a much greater affinity for and could displace Ex 4877 from renal receptors was excluded by the finding that the action of HCTZ was still blocked in dogs that had responded fully to furosemide. These results might be explained by postulating that the two diuretics act at different tubular segments of the nephron, but this possibility is remote, for most published data indicate that their sites of action overlap. The most tenable conclusion is that furosemide has its own distinctive mode of action.