Elevated levels of plasma atrial natriuretic peptide in Bartter's syndrome fall to normal with indomethacin: implications for atrial natriuretic peptide regulation in man.

Plasma atrial natriuretic peptide (ANP) levels were inappropriately elevated in Bartter's syndrome, in contrast with appropriately low levels in patients with Addison's disease and bulimia, with similar hyper-reninaemia and volume contraction. Inappropriate overproduction of ANP in Bartter's syndrome may be important in the pathophysiology. Prostaglandin inhibitors cause sodium retention and might be expected to increase ANP levels, based on their volume effects. Surprisingly, therefore, both indomethacin and aspirin lowered elevated levels of ANP in Bartter's syndrome to normal, indomethacin achieving this within 24 h. Single doses of indomethacin and aspirin also lowered plasma ANP levels in normal subjects. Saline infusion in Bartter's syndrome increased already-elevated levels of ANP further. When repeated during indomethacin treatment, despite suppression of basal levels to normal, even higher levels were achieved in three of four subjects. These results are consistent with a role for prostaglandins in ANP release in man, but suggest that another mechanism is also operative. They may help to explain the variable renal effects of prostaglandin inhibition.