Differential regulation of collecting duct Na+, K+-ATPase and K+ excretion by furosemide and piretanide: role of bradykinin.
In response to chronic treatment with furosemide, collecting ducts adapt their function to the initial loss of Na+ to prevent further Na+ loss and extracellular volume decrease. This adaptation, which includes the overexpression of Na+, K+-ATPase, is thought to account for most of the kaliuretic effect of furosemide. Because piretanide is reported to be less kaliuretic than equidiuretic doses of furosemide, the authors compared the effects of 1-wk treatment with the two loop diuretics on urinary potassium excretion and on Na+, K+-ATPase activity in the collecting duct. At equidiuretic and equinatriuretic doses, furosemide increased urinary potassium excretion as well as collecting duct Na+, K+-ATPase activity, whereas piretanide had no effect on either parameter. These effects of furosemide were curtailed by concomitant administration of the angiotensin-converting enzyme inhibitor enalapril, but they were not altered either by clamping changes in plasma aldosterone or by blocking type I angiotensin receptors. Treatment with the antagonist of bradykinin B2 receptors Hoe140 mimicked the two effects of furosemide. In addition, the effects of Hoe140 and furosemide were not additive. Finally, piretanide increased urinary bradykinin excretion, whereas furosemide did not. These results suggest that induction of collecting duct Na+, K+-ATPase (a) accounts for the kaliuretic effect of furosemide, (b) is independent of the renin/angiotensin/aldosterone system, (c) results from increased Na+ delivery to the collecting duct and enhanced intracellular Na+ concentration, and (d) is prevented in piretanide treated rats by increased bradykinin production that may limit apical Na+ entry in collecting duct principal cells.
Buffin-Meyer
Bénédicte
B
Laboratoire de Physiologie et Génomique des Cellules Rénales (UMR 7134 CNRS/Université Paris 6), Institut des Cordeliers, Paris, France. benedicte.buffin-meyer@toulouse.inserm.fr
Younes-Ibrahim
Mauricio
M
El Mernissi
Ghazi
G
Cheval
Lydie
L
Marsy
Sophie
S
Grima
Michèle
M
Girolami
Jean-Pierre
JP
Doucet
Alain
A
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D011188:Potassium / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
D004232:Diuretics; D013449:Sulfonamides; D005665:Furosemide; C015451:piretanide; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D001920:Bradykinin