Bartter's Syndrome: Physiological and Pharmacological Studies

Six siblings with Bartter's syndrome were studied. Increasedurinary Immunoreactlve prostaglandin E (iPgE) was correctedby administration of the prostaglandin synthetase inhibitors,Indomethacin, ibuprofen and meclofenamate. In addition, plasmapotassium rose, plasma renln activity and angiotensin resistancedecreased, and the exaggerated natriuresis following salineloading was abolished. Increased urinary iPgE also became normalfollowing the phospholipase inhibitor, mepacrine, but the otherabnormalities remained unaltered. The kallikrein inhibitor,aprotlnin, did not alter urinary iPgE, plasma potassium or electrolytebalance. During hypotonic saline infusion, proximal tubularsodium reabsorption was normal or increased. Free water clearanceand the percentage of distaliy delivered sodium which was reabsorbedwere, however, significantly decreased. The results suggestthat neither the increased renal PgE production nor the hyper-bradykinlnemiaseen in Bartter's syndrome play a major role in its pathogenesis,or manifestations, and that the effects of the prostaglandinsynthetase inhibitors on the syndrome are non-specific. Theresults and relevant literature are analysed in an attempt toidentify the initial defect in the interrelated sequence ofevents. The data are compatible with an intrarenal defect insodium transport, leading to increased sodium delivery to thedistal tubule, with secondary hyperreninemia, hypokalemia andelevated iPgE excretion.