Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis.
1. To further explore the Na(+)-retaining effect of indomethacin along the whole length of the nephron, the Na(+)-K(+)-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2. 2. Indomethacin increased Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (+24%, P < 0.001 versus control), proximal straight tubule (+75%, P < 0.001 versus control), medullary thick ascending limb (+68%, P < 0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P < 0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na(+)-K(+)-ATPase activity by -42% (P < 0.001 versus control). 3. Indomethacin also strongly increased Na(+)-K(+)-ATPase activity in the cortical collecting duct of adrenalectomized rats. 4. In isolated tubules from control rats, prostaglandin E2 reduced Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (-33%, P < 0.05), proximal straight tubule (-60%, P < 0.001), medullary thick ascending limb (-43%, P < 0.001), cortical thick ascending limb (-25%, P < 0.001) and cortical collecting duct (-45%, P < 0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na(+)-K(+)-ATPase activity (+32%, P < 0.05). 5. That these changes in Na(+)-K(+)-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.
Scherzer
P
P
Nephrology Service, Hadassah University Hospital, Jerusalem, Israel.
Wald
H
H
Rubinger
D
D
Popovtzer
M M
MM
D000315:Adrenalectomy; D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D007213:Indomethacin