Bartter's syndrome: physiological and pharmacological studies.
Six siblings with Bartter's syndrome were studied. Increased urinary immunoreactive prostaglandin E (iPgE) was corrected by administration of the prostaglandin synthetase inhibitors, indomethacin, ibuprofen and meclofenamate. In addition, plasma potassium rose, plasma renin activity and angiotensin resistance decreased, and the exaggerated natriuresis following saline loading was abolished. Increased urinary iPgE also became normal following the phospholipase inhibitor, mepacrine, but the other abnormalities remained unaltered. The kallikrein inhibitor, aprotinin, did not alter urinary iPgE, plasma potassium or electrolyte balance. During hypotonic saline infusion, proximal tubular potassium or electrolyte balance. During hypotonic saline infusion, proximal tubular sodium reabsorption was normal or increased. Free water clearance and the percentage of distally delivered sodium which was reabsorbed were, however, significantly decreased. The results suggest that neither the increased renal PgE production nor the hyperbradykininemia seen in Bartter's syndrome play a major role in its pathogenesis, or manifestations, and that the effects of the prostaglandin synthetase inhibitors on the syndrome are non-specific. The results and relevant literature are analysed in an attempt to identify the initial defect in the interrelated sequence of events. The data are compatible with an intrarenal defect in sodium transport, leading to increased sodium delivery to the distal tubule, with secondary hyperreninemia, hypokalemia and elevated iPgE excretion.
D000328:Adult; D000368:Aged; D000804:Angiotensin II; D007611:Aprotinin / Q000627:therapeutic use; D001477:Bartter Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D004231:Diuresis / Q000187:drug effects; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000503:physiopathology*; D008297:Male; D008469:Meclofenamic Acid / Q000627:therapeutic use; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D011458:Prostaglandins E / Q000652:urine; D011796:Quinacrine / Q000627:therapeutic use; D012965:Sodium Chloride
D011458:Prostaglandins E; D000804:Angiotensin II; D012965:Sodium Chloride; D008469:Meclofenamic Acid; D007611:Aprotinin; D011796:Quinacrine