AJP - Renal Physiology, Vol 244, Issue 6 666-F673, Copyright © 1983 by American Physiological Society
Furosemide action on collecting ducts: effect of prostaglandin synthesis inhibition
D. R. Wilson, U. Honrath and H. Sonnenberg
The effect of furosemide on inner medullary collecting duct chloride
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 chloride, sodium, and water
reabsorption in the inner medullary collecting duct. Rats given
indomethacin or meclofenamate before and during furosemide administration
showed marked reduction of the chloriuresis, natriuresis, and diuresis.
Reduced delivery of sodium and chloride 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. The results indicate that furosemide
inhibits medullary collecting duct reabsorption of chloride, sodium, and
water 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.
