Role of prostaglandins in the pathogenesis of Bartter's syndrome.
Increased renal prostaglandins activated by beta-catecholamines could produce renal tubular sodium wasting and angiotensin pressor resistance observed in Bartter's syndrome. We therefore measured plasma renin activity (PRA), aldosterone and prostaglandin A (PGA) by radioimmunoassay, and body composition by isotope dilution prior to and following beta-adrenergic blockade with propranolol (200 mg/day for 4 days) and prostaglandin synthesis inhibition by indomethacin (200 mg/day for 4 days) in a patient with Bartter's syndrome on a 250 meq sodium diet. After the administration of propranolol, body weight increased 3 kg, daily urine sodium decreased within 24 hours from 230 to 64 meq, and urine potassium from 102 to 45 meq, but PRA and the aldosterone level remained elevated. With the administration of indomethacin, body weight increased 5 kg, daily urinary sodium decreased within 24 hours to 11meq and urine potassium to 16 meq, PRA (normal less than 3 ng/100 ml/hour) decreased from 55 to 4.3 ng/ml/hour, plasma aldosterone (normal less than 8 ng/100 ml) from 74.1 to 3.6 ng/100 ml, and whole blood PGA (normal 546 +/- 307 pg/ml) decreased from 1,390 and 945 to 86 pg/ml. After the administration of propranolol or indomethacin, exchangeable sodium, total body water, extracellular volume and plasma volume all increased from less than to greater than predicted, and pressor resistance to angiotensin was normalized. These results suggest that Bartter's syndrome results from beta adrenergic and prostaglandin-mediated proximal tubular rejection of sodium leading to increased distal sodium-potassium exchange.
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology; D001477:Bartter Syndrome / Q000097:blood / Q000503:physiopathology*; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006929:Hyperaldosteronism / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007223:Infant; D008297:Male; D011188:Potassium / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011454:Prostaglandins A / Q000097:blood / Q000502:physiology*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D011454:Prostaglandins A; D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D011433:Propranolol; D012083:Renin; D011188:Potassium; D007213:Indomethacin