Evidence that circulating 6keto prostaglandin E1 causes the platelet defect of Bartter's syndrome.
Bartter's syndrome is associated with activation of prostaglandin metabolism. In the present study we provide several lines of evidence that a circulating metabolite of prostacyclin, 6ketoPGE1 is responsible for a defect in platelet function present in patients with Bartter's syndrome. In platelet aggregometry studies, plasma from patients contained platelet inhibitory activity which was fully neutralized by coincubation with antibody directed against 6ketoPGE1. Fractionation of lipophilic extracts of plasma by high pressure liquid chromatography yielded a platelet inhibitory fraction which comigrated with authentic 6ketoPGE1 and was neutralized by anti 6ketoPGE1 antibody. Lastly, direct measure of the plasma concentration of 6ketoPGE1 by specific radioimmunoassay indicates a 2-fold increase in patients with Bartter's syndrome (133 +/- 9.1 vs 60.7 +/- 12.3 picograms/ml; p less than 025). These studies provide firm evidence that the platelet dysfunction present in patients with Bartter's syndrome is attributable to an increase in the plasma concentration of 6ketoPGE1. In addition, these data provide further evidence in support of the centrality of activation of prostaglandin metabolism in the pathophysiology of Bartter's syndrome.
Clive
D M
DM
Department of Medicine, University of Massachusetts Medical School, Worcester 01655.
Stoff
J S
JS
Cardi
M
M
MacIntyre
D E
DE
Brown
R S
RS
Salzman
E W
EW
D000328:Adult; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000276:immunology / Q000502:physiology; D000906:Antibodies / Q000276:immunology; D001477:Bartter Syndrome / Q000209:etiology*; D001792:Blood Platelets / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D010974:Platelet Aggregation; D011863:Radioimmunoassay
D000906:Antibodies; C022950:6-ketoprostaglandin E1; D000527:Alprostadil