Effects of indomethacin on epidermal growth factor-induced renal responses in sheep

1. The effects of indomethacin (an inhibitor of prostaglandin synthesis) on the renal responses to epidermal growth factor (EGF) were investigated in conscious sheep. 2. Ewes (n = 5 per group) received an i.v. saline infusion (150 mL/day) for days 1-8, followed by either vehicle control, 15 micrograms/h EGF, 2 mg/kg per day indomethacin or 15 micrograms/h EGF with 2 mg/kg per day indomethacin in 150 mL/day saline, i.v., over days 9-12. All ewes subsequently received an i.v. saline infusion (150 mL/day) over days 13-20. 3. Polydipsia, diuresis, transient natriuresis and reduced urine osmolality occurred during EGF treatment alone. There was no effect of EGF on fluid balance, plasma electrolyte or hormone concentrations, plasma osmolality or haematocrit or on the urinary excretion of potassium. 4. Simultaneous infusion of indomethacin with EGF attenuated (P < 0.05) the stimulatory effects of EGF infusion alone on urine volume, water intake, natriuresis and urine osmolality. 5. We conclude that prostaglandins may be involved in the diuretic/natriuretic effects of EGF, but may not be the sole mechanism involved.