The effect of indomethacin on the renal response to arginine vasopressin in man

Abstract

The renal response to graded intravenous infusions of arginine vasopressin (AVP) was investigated in a two part study in six volunteers. First, under maximal water diuresis, seven control incremental infusions of AVP were given from zero to 12 fmol min-1 kg-1. Second, the AVP infusions were repeated after pretreatment with indomethacin, 150 mg daily for 36 h. After the AVP infusions, plasma AVP concentrations did not change significantly and remained within the physiological range; in contrast, urinary AVP excretion rate increased steadily. Indomethacin did not alter the plasma or urinary concentrations of AVP. AVP caused a fall in urine flow rate from a state of maximal diuresis to one of maximal antidiuresis. After indomethacin, fractional free water clearance was reduced by an average of 26% at the zero, 2 and 4 fmol min-1 kg-1 infusion rates of AVP. A significant increase in fractional sodium clearance of approximately 50% occurred during the AVP infusions, which was abolished after pretreatment with indomethacin. After indomethacin, urinary prostaglandin E2 (PGE2) excretion rate was reduced by an average of 40% at the zero and 2 fmol min-1 kg-1 infusion rates of AVP. At higher AVP infusion rates, no significant inhibition of PGE2 was observed. Urinary kallikrein excretion rate decreased steadily to one-third of its original value after AVP and this change remained unaltered by indomethacin. The findings show that infusions of AVP, resulting in plasma concentrations in the physiological range, evoke a maximal antidiuretic response, which is accompanied by natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)