Mechanism of the effects of furosemide on renin secretion in anesthetized dogs.

Furosemide was administered to anesthetized dogs in priming doses of 0.1, 0.5, or 2.5 mg/kg followed by the same amounts per hour as infusion. When sodium and water balances were maintained constant by the continuous replacement of urinary losses with isotonic saline, the renal venous renin activity (and renin release) was not altered by the 0.1 mg/kg dose but was significantly increased by the two larger doses. This increase was manifest within 5 to 10 minutes. The larger doses also increased mean arterial pressure but did not change plasma sodium or glomerular filtration rate. Renal plasma flow was increased by the 2.5 mg/kg dose but not by the 0.5 mg/kg. In another group of dogs in which salt depletion was allowed to occur, 0.1 mg/kg produced an increased renin release within 30 minutes; this increase was completely reversed by the replacement of sodium and water losses. In this group of dogs, the glomerular filtration rate decreased and then returned to control values after restoration of fluid balance. It is hypothesized that the two higher doses of furosemide stimulated renin release by directly inhibiting macula densa sodium transport, and that the reported effects of all natriuretics can be explained in terms of a single macula densa theory. ADDITIONAL