Correction of increased prostacyclin synthesis in Bartter's syndrome by indomethacin 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-PGF1 alpha and thromboxane B2, respectively, in five patients. The prostaglandin metabolites 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-PGF1 alpha 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-PGF1 alpha by 43% and that of thromboxane B2 by 46%. It is suggested that the increase in prostacyclin production is responsible for both the hyperreninemia and and the other endocrine derangements as well as the hyporesponsiveness of blood pressure to intravenous infusion of vasopressors in patients with Bartter's syndrome.     

Dependence of centriole formation on protein synthesis

Electron microscope observations were made of rat peroneal nerve after crushing using intravenously injected horseradish peroxidase (HRP) as a tracer protein to indicate changes in vascular permeability. At 1/2 h and 2 d after the crush there was gross leakage of HRP from damaged capillaries at the site of injury but none from vessels above or below this. Ultrastructurally vessels at the site of crush showed broken and separated endothelial cells. Proximally and distally there was little abnormal in the vessel walls; vesicles containing HRP were absent and tight-junctions between cells remained intact. Twenty-one days after the crush, leakage of HRP was found both at the site of crush and along the distal segment. The only change in vessel walls was an obvious increase in vesicles filled with HRP. Tracer was also found both in perivascular locations and throughout the endoneurial space.