Furosemide increases urine 6-keto-prostaglandin F1 alpha. Relation to natriuresis, vasodilation, and renin release.

While previous studies have shown that prostaglandins (PG) mediate the renal vasodilating and renin-releasing actions of furosemide, the dose-response relationship has not been defined nor has the specific PG involved. Prostacyclin (PGIj) is synthesized in the renal cortex, is a vasodilator, can release renin and, therefore, could mediate these actions of furosemide. The authors measured urinary excretion of the PGI2 hydrolysis product 6-keto prostaglandin Fla (U6kV) in response to increasing intravenous bolus doses of furosemide in anesthetized dogs. Furosemide 0.1 mg/kg increased urine volume (V) and sodium excretion (UNaV) compared to control dogs, but did not change U6kV, p-aminohippurate clearance (CPAH), or plasma renin activity (PRA). A higher dose (1.0 mg/ kg) increased V, UNaV, U6kV (23.4 ± 11.0 to 56.5 ± 18.7 ng/15 min, p < 0.05), CPAH (121 ± 40 to 304 ± 80 ml/min, p < 0.05), and PRA (5.4 ± 2.2 to 11.7 ± 4.4, p < 0.05). There was no correlation between U6kV and V or UNaV, but correlations existed between U6kV and CPAH (r = 0.81, p < 0.001) and between the percent increase of U6k V and the percent increase of PRA fol lowing each dose of furosemide (r = 0.59, p < 0.05). In separate experiments, we assessed the effects of increasing renal blood flow (RBF) on U6kV, by infusing the PG-independent vasodilator secretin into a renal artery. RBF of the single kidney increased from 124 ± 32 to 202 ± 21 ml/min (p < 0.01) and CPAH from 56 ± 18 to 83 ± 42 ml/min (p < 0.05), but U6kV did not change. Indomethacin reduced U6kV but did not affect secretin-induced increases in RBF or CPAH. The results indicate that furosemideinduced natriuresis occurs at low doses and in the absence of an effect on U6kV. In contrast, furosemide induced vasodilation and renin release required higher doses and were associated with increased U6kV. Because secretin can increase RBF without changing U6kV, we suggest that furosemide-induced increases in U6kV are not secondary to increased RBF. Rather, it appears that furosemide releases renal PGI2 which, in part, mediates vasodilation and renin release, and was excreted in urine as 6-keto-prostaglandin Fla. (Hypertension 4: 634-641, 1982)