We examined the hypothesis that the vascular abnormalities of
Bartter's syndrome are due to excess production of
prostaglandin. Balance studies and vascular reactivity studies were performed before and after
indomethacin (200 mg/day) in a patient with well-documented
Bartter's syndrome. During
indomethacin,
potassium balance became positive, serum
potassium rose from 2.1--3 mEq/1 in the absence of
potassium supplementation, plasma
renin activity decreased from 55--3.2 ng/day and peripheral plasma
PGA-like activity fell from 1460 +/- 220 to 456 +/- 71 pg/ml. Before
indomethacin, forearm
vasoconstrictor responses to brachial arterial infusions of
angiotensin II,
norepinephrine and to neurogenic reflex stimulation elicited by lower body suction were greatly depressed compared to those of normal subjects. During
indomethacin these responses were restored to normal. The dose of intravenous
angiotensin II required to increase diastolic blood pressure 20 mm Hg decreased from 160--30 ng/kg/min. These data support the hypothesis that the vascular insensitivity to exogenous
angiotensin II,
norepinephrine and to neurogenic reflex stimulation observed in this patient with
Bartter's syndrome is due to excess
prostaglandin. Moreover, stimulation of the renin-angiotensin-aldosterone system in this syndrome appears to be a compensatory adaptation to excess
prostaglandin production.