Hypokalemia and prostaglandin overproduction in Bartter's syndrome.
In 2 adult patients with Bartter's syndrome, in whom chloride reabsorption at the diluting segment of the nephron was markedly reduced, serum potassium concentration could be improved with oral administration of a large amount of potassium chloride. In both cases, improvement of serum potassium levels with oral potassium load resulted in an increase in plasma renin activity (PRA) and plasma aldosterone concentration (PAC), a decrease in urinary excretion of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), and an improvement of pressor responsiveness to angiotensin II and norepinephrine. Treatment with indomethacin also improved the pressor responsiveness to angiotensin II and norepinephrine, but this occurred in association with a decrease in PRA, PAC and urinary excretion of PGE2 and PGF2 alpha. These results indicated that an event at the renal tubular level leading to potassium depletion is the most proximal pathogenetic defect in Bartter's syndrome, and that this in turn contributes to excessive prostaglandin production leading further to the decreased pressor responsiveness to vasoactive substances.
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000627:therapeutic use; D001477:Bartter Syndrome / Q000150:complications / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000503:physiopathology*; D007008:Hypokalemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000627:therapeutic use; D011188:Potassium / Q000097:blood; D011189:Potassium Chloride / Q000627:therapeutic use*; D011458:Prostaglandins E / Q000652:urine*; D011460:Prostaglandins F / Q000652:urine*; D012083:Renin / Q000097:blood
D011458:Prostaglandins E; D011460:Prostaglandins F; D000804:Angiotensin II; D000450:Aldosterone; D011189:Potassium Chloride; D015237:Dinoprost; D012083:Renin; D015232:Dinoprostone; D011188:Potassium; D009638:Norepinephrine; D007213:Indomethacin