Inhibition of the kallikrein-kinin system and vascular reactivity in Bartter's syndrome.
To study the significance of the increased activity of the kallikrein-kinin system described in patients with Bartter's syndrome, we investigated the pressor response to infused angiotensin II in four patients with the syndrome receiving no treatment and during the administration of aprotinin and of indomethacin. Five normal subjects served as controls. Aprotinin is a proteolytic enzyme that inhibits the formation of kinins by inhibiting plasma and glandular kallikrein. Indomethacin, a prostaglandin-synthesis inhibitor, can also inhibit the kallikrein-kinin system and normalizes vascular responsiveness to angiotensin II in Bartter's syndrome. All patients had increased urinary kallikrein and prostaglandin E2 concentrations. Aprotinin significantly decreased the dose of infused angiotensin II required to induce a 20 mm Hg increase in diastolic blood pressure, from 11 +/- 4 ng/kg/min to 7.0 +/- 2.0 ng/kg/min (mean +/- SD; p less than 0.05) in normal subjects and from 135 +/- 57 ng/kg/min to 70 +/- 26 ng/kg/min (p less than 0.05) in the patients with Bartter's syndrome, without significantly changing plasma renin activity, mean control blood pressure, or urinary prostaglandin E2 concentration. Indomethacin normalized the pressor response to angiotensin II in three patients who had been pretreated for 4 days (pressor dose, 10 ng/kg/min) but not in one patient who received a single oral dose of indomethacin 5 hours before the test. Our results suggest that inhibition of the kallikrein-kinin system alone accounts for approximately a 50% decrease in vascular resistance to the pressor effect of angiotensin II in Bartter's syndrome, while additional suppression of prostaglandins entirely normalizes the vascular response to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
J A
JA
Rodriguez-Portales
J M
JM
Lopez-Moreno
D
D
Mahana
D000328:Adult; D000804:Angiotensin II; D007611:Aprotinin / Q000494:pharmacology; D001477:Bartter Syndrome / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007610:Kallikreins / Q000502:physiology*; D007705:Kinins / Q000502:physiology*; D008297:Male; D014655:Vascular Resistance / Q000187:drug effects
D007705:Kinins; D000804:Angiotensin II; D007611:Aprotinin; D007610:Kallikreins; D007213:Indomethacin