The kallikrein-kinin system in Bartter's syndrome and its response to prostaglandin synthetase inhibition.
The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3+/-5.3 (S.E.M.) ng/ml per h to 3.3+/-1.1 ng/ml per h, mean plasma bradykinin (patients recumbent) from 15.4+/-4.4 ng/ml to 3.9+/-0.9 ng/ml, mean urinary kallikrein excretion from 24.8+/-3.2 tosyl-arginine-methyl ester units (TU)/day to 12.4+/-2.0 TU/day, but increased mean urinary kinin excretion from 3.8+/-1.3 mug/day to 8.5+/-2.5 mug/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for urinary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The results suggest that, in Bartter's syndrome, prostaglandins mediate the low urinary kinins and the high plasma bradykinin, and that urinary kallikrein, which is aldosterone dependent, does not control kinin excretion. The high plasma bradykinin may be a cause of the pressor hyporesponsiveness to angiotensin II which characterizes the syndrome.
D000293:Adolescent; D000328:Adult; D001477:Bartter Syndrome / Q000378:metabolism*; D001920:Bradykinin / Q000097:blood; D002648:Child; D016861:Cyclooxygenase Inhibitors; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism*; D007610:Kallikreins / Q000378:metabolism* / Q000652:urine; D007705:Kinins / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D011288:Prekallikrein / Q000032:analysis
D016861:Cyclooxygenase Inhibitors; D007705:Kinins; D011288:Prekallikrein; D007610:Kallikreins; D001920:Bradykinin