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.