Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs.
The present study was performed to determine the tubular sites of nitrite and nitrate (NO) reabsorption and the effects of furosemide on the renal handling of NOx in anesthetized dogs, using renal clearance and stop-flow methods. Furosemide (2 mg/kg, i.v.) increased the urinary excretion rates of Na+ (U(Na+)V) and NOx (U(NOx)V) with a reduction of tubular reabsorption rates of Na+ and NOx. During inhibition of renal nitric oxide (NO) synthesis by an intrarenal infusion of L-nitro arginine (30 microg/kg-min), furosemide also increased U(NOx)V and decreased tubular reabsorption rate of NOx from 96.5+/-0.8% to 86.6+/-1.7%. An intravenous infusion of 10% mannitol (0.5 ml/kg-min) also increased both U(Na+)V and U(NOx)V. In addition, after furosemide administration or mannitol infusion. U(NOx)V was correlated with U(Na+)V. In stop-flow experiments, the distal dip in NOx curve was observed and the site of the dip in NOx curve was identical to that of Na+ curve. Furosemide shifted upward the U/P(Na+)/U/P(Cr) and U/P(NOx)/U/P(Cr) at the distal dip, indicating inhibition of Na+ and NOx reabsorption at distal tubules. These results indicate that more than 96% of the filtered NOx is reabsorbed in the renal tubules, and that the tubular handling of NOx is very close to that of Na+. In addition, the stop-flow experiments demonstrate that furosemide inhibited the reabsorption of NOx as well as Na+ at the distal tubule.
Rahma
M
M
Department of Pharmacology, Kagawa Medical University, Japan. yakuri@kms.ac.jp
Kimura
S
S
Yoneyama
H
H
Kosaka
H
H
Nishiyama
A
A
Fukui
T
T
Abe
Y
Y
D000758:Anesthesia; D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004234:Diuretics, Osmotic / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008353:Mannitol / Q000494:pharmacology; D009566:Nitrates / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D004232:Diuretics; D004234:Diuretics, Osmotic; D004791:Enzyme Inhibitors; D009566:Nitrates; D019335:Nitroarginine; D008353:Mannitol; D005665:Furosemide; D012964:Sodium; D019001:Nitric Oxide Synthase