Effect of amiloride on the compensatory renal growth that follows uninephrectomy in mice.
The increase in contralateral kidney mass that follows the removal of one kidney is caused primarily by the hypertrophy and, to a lesser extent, the hyperplasia of tubule cells. Amiloride inhibits the proliferation of cells in tissue culture environments and diminishes compensatory hyperplasia of liver cells after partial hepatectomy. In the current study, we determined the extent to which amiloride diminished the compensatory increase in contralateral kidney weight and protein content after uninephrectomy. Caworth Farms mice, 3 to 4 months of age, received amiloride by daily intraperitoneal injection for 7 days before the left kidney was removed and for an additional 4 days after nephrectomy. Four days after uninephrectomy, compensatory hypertrophy was quantified by the increase in weight and protein content of the right kidney in comparison with the left (R - L divided by L x 100; [weight] +24.7% +/- 2.9% and [protein] +20.6% +/- 4.4%). Treatment with amiloride reversibly reduced the compensatory increase in kidney weight and protein content (dose required to achieve 50% inhibition, 11.4 and 2.4 mg/kg/day, respectively). Hexamethylene amiloride, an analog with weak affinity for conductive Na+ channels and high affinity for Na+-H+ exchangers, had no effect on compensatory hypertrophy. Spironolactone, a natriuretic and antikaliuretic agent of potency similar to that of amiloride, but with a different cellular mechanism of action, had no effect on compensatory hypertrophy. We conclude that amiloride reversibly blunts the compensatory renal hypertrophy after uninephrectomy in mice by mechanisms that appear to be separate from the drug's effects to block Na+-H+ exchange and transepithelial Na+ and K+ transport.
Grantham
J J
JJ
Department of Medicine, University of Kansas School of Medicine, Kansas City 66103.
Grantham
J A
JA
Donoso
V S
VS
Cragoe
E J
EJ
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000254:growth & development*; D008297:Male; D051379:Mice; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D013148:Spironolactone / Q000494:pharmacology
D002352:Carrier Proteins; D011506:Proteins; D017923:Sodium-Hydrogen Exchangers; C057360:5-(N,N-hexamethylene)amiloride; D013148:Spironolactone; D000584:Amiloride; D012964:Sodium; D011188:Potassium