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A Japanese family in which a father, daughter and son had hypokalemia and hyperreninemia was investigated. Both father and daughter had reduced vascular sensitivity to angiotensin II; in addition, the daughter had juxtaglomerular cell hyperplasia and dwarf glomeruli. These features are consistent with Bartter's syndrome occurring in 2 successive generations in 1 family. The 12-year-old girl had growth retardation in spite of normal growth hormone secretion. No chromosomal abnormalities were found. Indomethacin administration to this patient in doses sufficient to reduce urinary prostaglandin excretion resulted in a marked improvement of polydipsia and polyuria, and an increase in serum sodium, potassium and chloride concentrations. Even though plasma aldosterone concentrations were reduced to within the normal range, serum potassium concentrations remained low, and plasma renin activity (PRA) remained elevated. Thus it is not likely that hypokalemia is induced only by aldosteronism. These results suggest that prostaglandins are the major determinant of polydipsia, polyuria and high plasma aldosterone levels and contribute to the hypokalemia observed in this patient. However, the failure of complete correction of the hypokalemia and the persistence of the raised PRA with a significant reduction of the prostaglandins suggest the possibility that additional factors are involved in the pathogenesis of Bartter's syndrome.

A child presenting with the characteristic biochemical findings of Bartter's syndrome is described. Short-term follow-up showed a satisfactory response to a prostaglandin synthetase inhibitor.

It has been claimed that in patients with Bartter's syndrome, enhanced prostaglandin synthesis causes the blunted vasopressor response to angiotensin II. The present study was undertaken to test this hypothesis by administering indomethacin to a patient with Bartter's syndrome. In domethacin corrected the subnormal pressor response to angiotensin II and lowered plasma renin activity from 115 to 15 ng/ml/hr. This effect was associated with renal sodium retention and a 7% increase in body weight. In contrast, when indomethacin was given but the sodium retention prevented by concomitant administration of furosemide, the blunted vasopressor response to angiotensin II and the hyperreninemia were not corrected. It is concluded that the effectiveness of indomethacin to correct the hyperreninemia and the blunted vasopressor to angiotensin II in the preset patient was due in large part to the ability of the drug to correct sodium balance rather than by inhibition of prostaglandin synthesis.

Two patients with Bartter's syndrome were treated with indomethacin (2 mg/kg/day). The administration of the drug resulted in weight gain; a decrease in the rate of urinary excretion of sodium and inorganic phosphate suggesting an increase in proximal tubular reabsorption; an increase in serum potassium concentration, with a transient decrease in the rate of urinary potassium excretion in one patient; and a decrease in plasma renin activity and in the rate of urinary aldosterone excretion. Since indomethacin has been shown to inhibit prostaglandin synthetase, these observations support the hypothesis that prostaglandin excess is a basic pathogenic mechanism in Bartter's syndrome.