Correction of increased prostacyclin synthesis in Bartter's syndrome by indometracin treatment

The role of prostacyclin and thromboxane A2 in the pathogenesis of Bartter's syndrome was investigated by measurement of the urinary excretion of 6-keto-PGF_1α and thromboxane B₂, respectively, in five patients. The prostaglandin metaeolites were extracted from urine by a reproducible method and measured by specific radioimmunoassays. The patients with Bartter's syndrome excreted about four-times as much 6-keto-PGF_1α as the normal controls.In contrast, there was no significant difference in the urinary excretion of thromboxane B₂ between the patients and the controls. In a second part of the study, three patients were treated with indomethacin (150 mg/day for four days), an inhibitor of prostaglandin synthesis. This regimen suppressed urinary excretion of 6-keto-PGF by 437 and that of thromboxane B₂ by 467. It is suggested that the increase in prostacyclin production is responsible for both the hyperreninemia and the other endocrine derangements as well as the hyporesponsiveness of blood pressure to intravenous infusion of vasopressors in patients with Bartter's syndrome.