Chronic indomethacin increases rabbit cortical collecting tubule Na+-K+-ATPase activity.
To help determine whether prostaglandin-mediated inhibition of transport in the isolated rabbit cortical collecting tubule (CCT) is related to a suppression of sodium pump activity, adrenalectomized rabbits on replacement dexamethasone were treated for 3 days with vehicle or the prostaglandin inhibitor, indomethacin. On the day of death, rabbits treated with indomethacin had a significantly reduced urinary prostaglandin E2 (PGE2) excretion rate compared with vehicle-treated animals (107 +/- 7 vs. 415 +/- 129 ng.kg body wt-1.day-1, indomethacin vs. vehicle, P less than 0.05). In addition, CCTs obtained from indomethacin-treated rabbits had a significantly higher Na+-K+-ATPase activity than controls (2.66 +/- 0.33 vs. 1.17 +/- 0.33 mol Pi.kg dry wt-1.h-1, 37 degrees C, P less than 0.005); Mg-ATPase activity was invariant. Despite the elevated CCT Na+-K+-ATPase activity, there was no evidence of a sustained increase in Na reabsorption and/or K excretion by the kidney. Thus at death, the fractional excretions of Na and K, urinary Na/K ratios and plasma K values in rabbits given indomethacin were not significantly different from control values. There was also no evidence for a direct effect of either indomethacin or PGE2 on Na+-K+-ATPase activity when added directly to CCT broken-cell assays. Therefore in vivo chronic indomethacin administration leads to a rise in CCT Na+-K+-ATPase activity, which is coincident with a fall in urinary PGE2, suggesting that endogenous PGE2 may suppress the activity of this enzyme by a cell-mediated process.
Cordova
H R
HR
University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas 75235.
Kokko
J P
JP
Marver
D
D
D000311:Adrenal Glands / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D015232:Dinoprostone / Q000652:urine; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D007684:Kidney Tubules / Q000201:enzymology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000201:enzymology*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D007213:Indomethacin