Furosemide action on collecting ducts: effect of prostaglandin synthesis inhibition

Abstract

The effect of furosemide on inner medullary collecting duct Cl reabsorption has not been determined, and the blunting of furosemide action by drugs that inhibit prostaglandin synthesis, while known to occur, has not been examined in detail. The effect of indomethacin and meclofenamate on furosemide diuresis was studied in the rat using clearance and collecting duct microcatheterization methods. Furosemide-treated control animals showed complete inhibition of Cl, Na and H2O reabsorption in the inner medullary collecting duct. Rats given indomethacin or meclofenamte before and during furosemide administration showed marked reduction of the chloriuresis, natriuresis and diuresis. Reduced delivery of Na and Cl to the beginning of the inner medullary collecting duct, associated with a decrease in glomerular filtration rate and increased reabsorption in more proximal nephron segments, was largely responsible for the reduced natriuresis and chloriuresis during inhibition of prostaglandin synthesis. In addition, indomethacin increased collecting duct NaCl reabsorption toward normal, but meclofenamate showed no such effect. Furosemide inhibits medullary collecting duct reabsorption of Cl, Na and H2O in the rat. The blunting of diuretic action seen with inhibition of prostaglandin synthesis is largely, although not entirely, due to effects of indomethacin and meclofenamate on furosemide action at nephron sites proximal to the collecting duct.