INTERACTIONS OF SPIRONOLACTONE AND HYDROCHLOROTHIAZIDE WITH ASPIRIN IN THE RAT AND DOG

¹ Department of Pharmacology, Division of Biological Research, G.D. Searle and Company, Chicago, Illinois

The influence of orally administered aspirin on the five-hour diuretic responses of spironolactone (S) and hydrochlorothiazide (HC) was evaluated as follows: 25, 100 and 300 mg/kg of aspirin were given with 20 mg/kg of S and 5 mg/kg of HC in male Badger rats injected s.c. with 50 µg of deoxycorticosterone acetate. After i.m. injection of 10 µg d-aldosterone in female mongrel dogs, aspirin was given in a dosage of 8 mg/kg with S at 2 and 8 mg/kg. In the presence (rat) and absence (dog) of observed diuretic responses to aspirin per se, coadministration of S resulted in a significant reduction of its specific mineralocorticoid blocking properties. Aspirin/S dosage ratios of 4:1 (dog) and 5:1 (rat) induced a net potassium loss in the rat and decreased natriuresis in the dog and, as a consequence, reduced the index (urinary Na/K ratio) of spironolactone's pharmacological activity at the renal level. The interaction of HC and aspirin was of a relatively lower order of sensitivity (absent at a 5:1 dosage ratio) with additive effects initially upon K excretion and later upon urine and Na output.