Prostaglandins and the urinary concentrating defect in potassium-depleted rabbits.
Urinary prostaglandin E (UPGE) excretion increased significantly after 1 and 2 wk of potassium depletion (KD) in female New Zealand White rabbits on ad libitum water intake [UPGE control, 21.3 +/- 4.6 ng PGE/mg creatinine; 1 wk KD, 40.4 +/- 6.1 ng PGE/mg creatinine (P less than 0.01); 2 wk KD, 31.9 +/- 14.9 ng PGE/mg creatinine (P less than 0.05)]. In vivo prostaglandin inhibition with indomethacin or meclofenamate significantly increased urinary osmolality after 12 h of dehydration and exogenous vasopressin (1.25 U) from 794 +/- 59 to 1,163 +/- 113 mosmol/kgH2O (P less than 0.01). In vitro prostaglandin inhibition with indomethacin or meclofenamate corrected the antidiuretic hormone (ADH) unresponsiveness of isolated perfused cortical collecting tubules (CCTs) from KD rabbits. Furthermore, preincubation with pertussis toxin, an agent that inactivates the guanine nucleotide inhibitory (Ni) subunit of adenylate cyclase, normalized the ADH response of KD CCTs, suggesting that prostaglandins may attenuate ADH action on the CCT through activation of Ni and contribute to the urinary concentrating defect associated with KD.
Raymond
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Research Service, Audie L. Murphy Memorial Veteran's Hospital, San Antonio, Texas.
Lifschitz
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McKinney
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D037361:Adenylate Cyclase Toxin; D000818:Animals; D003681:Dehydration / Q000378:metabolism; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007671:Kidney Concentrating Ability; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism; D008433:Mathematics; D008469:Meclofenamic Acid / Q000494:pharmacology; D009994:Osmolar Concentration; D037342:Pertussis Toxin; D011191:Potassium Deficiency / Q000503:physiopathology / Q000652:urine*; D011458:Prostaglandins E / Q000652:urine*; D011817:Rabbits; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D011458:Prostaglandins E; D010566:Virulence Factors, Bordetella; D008469:Meclofenamic Acid; D037342:Pertussis Toxin; D007213:Indomethacin