INFLUENCE OF PROBENECID AND ALTERATIONS IN ACID-BASE BALANCE OF THE SALURETIC ACTIVITY OF FUROSEMIDE

¹ Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa

When furosemide was infused into the left renal artery at 1 µg/kg/minute it produced a significant ipsilateral increase in the excretion of sodium and water without affecting the rate of glomerular filtration. At this dosage, the response was usually limited to the infused kidney. Systemic administration of probenecid (50 mg/kg) inhibited the response to furosemide. These data demonstrate that furosemide induced natruresis is the result of a direct action upon the kidney. A direct tubular action is suggested by the lack of marked alterations in glomerular filtration rate. Inhibition of furosemide induced natruresis by probenecid suggests that adequate cellular concentration (and/or luminal concentration) rather than plasma concentration is a prerequisite to the natruretic action of this compound.

Alteration of plasma pH with hydrochloric acid or sodium bicarbonate did not appear to affect the response to furosemide. Increases in sodium excretion were matched by increases in chloride excretion in both conditions.

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