The role of chloride transport in the thick ascending limb in the pathogenesis of Bartter's syndrome.

Fractional chloride reabsorption in the thick ascending limb of the loop of Henle, measured by clearance techniques, is subnormal in patients with Bartter's syndrome. This defect is a marker for the syndrome and, presumably, is the cause of the supranormal tubular secretion of potassium that characterizes the disorder. The potassium depletion that results from excessive potassium excretion is probably the stimulus for the increased synthesis of prostacyclin by blood vessels and prostaglandin E2 by kidneys that occurs in Bartter's syndrome. The overproduction of prostaglandins mediates hyperreninemia, supranormal plasma bradykinin, supranormal plasma norepinephrine and vascular resistance to the pressor effects of angiotensin II and norepinephrine; treatment with a prostaglandin synthetase inhibitor corrects these abnormalities. Increases in angiotensin II and in norepinephrine appear to be compensatory changes, occurring in response to vasodilatation induced by vascular prostaglandins to maintain blood pressure. The hyperreninemia also stimulates production of aldosterone with aggravation of potassium loss.