The effect of indomethacin on basal and saline-stimulated plasma atrial natriuretic factor levels in normal man.
Surprisingly inappropriately high levels of plasma atrial natriuretic factor (ANF) in subjects with Bartter's syndrome are lowered by indomethacin therapy. Indomethacin in normal man causes sodium retention. One might therefore expect plasma ANF to increase in subjects taking indomethacin as a secondary phenomenon. On the other hand a decrease of plasma ANF in normal man similar to that reported in Bartter's subjects may explain the sodium retention caused by the drug in normals. We have studied plasma ANF before and during a two litre, four hour normal saline infusion in eight healthy male subjects both before and following five days of oral indomethacin. Plasma ANF basally was 4.2 +/- 0.9 pmol/l (mean +/- SEM) on no drug and 5.2 +/- 0.6 pmol/l on indomethacin (NS). It increased in response to saline in both studies (7.8 +/- 1.5 pmol/l after two litres of saline on control day; 10.6 +/- 1.5 pmol/l on the drug at the equivalent time, both p less than 0.05 vs basal value). Overall response to saline as assessed by the area under the curve above the basal value of hourly measurements, was not different in the two studies. Basal serum aldosterone and plasma renin activity were reduced by indomethacin. Urinary sodium excretion was not different between groups during the 12 hours before, four hours during and eight hours after the infusion. We have shown that indomethacin does not alter basal or saline stimulated plasma ANF in normal man, a finding in contrast to that reported in subjects with Bartter's syndrome. The sodium retention caused by indomethacin in normal man is not therefore due to a decrease of plasma ANF.
McKnight
J A
JA
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, Northern Ireland.
Roberts
G
G
Sheridan
B
B
Atkinson
A B
AB
D000284:Administration, Oral; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D001481:Basal Metabolism; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology*
D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D007213:Indomethacin