Effects of prostaglandin inhibition on the renal function curve during ovine pregnancy

Abstract

This study was designed to assess the influence of prostaglandins on the steady-state relationship of mean arterial pressure and urinary sodium excretion. Ten nonpregnant and nine pregnant ewes were chronically prepared with indwelling catheters and maintained in metabolism cages. All the ewes received a continuous intravenous infusion of indomethacin (5 mg/kg/day) for 24 days. Step increases in sodium intake (20, 100, 400, and 1200 mmol per day), each maintained for 6 days, were administered as a fixed dietary (20 mmol) component with the balance infused intravenously. Mean arterial pressure was continuously monitored. The renal function curves were constructed from the steady-state mean arterial pressure-urinary sodium excretion relationships after sodium balance was attained. Indomethacin inhibited urinary excretion of prostaglandin E2 by 62% +/- 4% in nonpregnant and 47% +/- 6% in pregnant ewes, and 6 keto-prostaglandin F1 alpha, the stable metabolite of prostaglandin I2, by 55% +/- 4% and 65% +/- 6% in nonpregnant and pregnant ewes, respectively. Blood volume was not affected by indomethacin or salt in either group. Plasma angiotensin II was suppressed less in pregnant ewes (60% vs 80%) by increases in salt intake. Chronic treatment with indomethacin did not alter the renal function curves of either nonpregnant or pregnant ewes. These results suggest that prostaglandins do not influence the steady-state relationship between mean arterial pressure and urinary sodium excretion in either nonpregnant or pregnant sheep.