Inhibition of thick ascending limb Na+-K+-ATPase activity in salt-loaded rats by furosemide.
To evaluate the role of increased thick ascending limb Na+-K+-ATPase activity in rats undergoing hypertonic salt loading, the following groups of rats were studied: 1) control rats, 2) rats receiving an oral hypertonic Na load for 7 days, and 3) rats receiving the same oral Na load as in group 2 plus a daily injection of 10 mg/100 g of furosemide ip for 7 days. Salt loading (group 2) was associated with increased glomerular filtration rate (GFR) and hence an increased filtered load of sodium. Plasma aldosterone levels were markedly decreased. Na+-K+-ATPase was unchanged in the proximal tubule [convoluted (PC) and straight (PS)], increased in the thick ascending limb of Henle's loop [outer medullary (OMTAL) and cortical (CTAL)] and decreased in the distal nephron [distal convoluted tubule (DCT) and cortical collecting duct (CCD)]. The renal corticomedullary gradient of solutes was markedly increased in the salt-loaded group. Salt loading plus furosemide for 7 days (group 3) was associated with severe dehydration and hypernatremia. GFR as well as plasma aldosterone levels were unchanged compared with control. Na+-K+-ATPase was significantly increased in the proximal tubule (PC and PS), markedly decreased in the thick ascending limb of Henle's loop (OMTAL and CTAL), increased in the DCT and unchanged in the CCD. The increase in the corticomedullary gradient caused by salt loading per se was abolished by treatment of salt-loaded rats with furosemide. These results indicate that treatment with furosemide prevents the preservation of water balance and of normal body fluid tonicity in rats undergoing hypertonic Na loading.(ABSTRACT TRUNCATED AT 250 WORDS)
Wald
H
H
Nephrology Services, Hadassah University Hospital, Jerusalem, Israel.
Scherzer
P
P
Popovtzer
M M
MM
D000818:Animals; D005665:Furosemide / Q000494:pharmacology*; D007684:Kidney Tubules / Q000201:enzymology*; D008138:Loop of Henle / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D012982:Sodium, Dietary / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014882:Water-Electrolyte Balance; D014883:Water-Electrolyte Imbalance / Q000201:enzymology / Q000517:prevention & control
D012982:Sodium, Dietary; D005665:Furosemide; D000254:Sodium-Potassium-Exchanging ATPase