Effects of Indomethacin on Epidermal Growth Factor‐induced Renal Responses in Sheep

Abstract

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.

Role of epidermal growth factor receptor in the pathogenesis and treatment of arterial hypertension

“…In contrast, infusion of betacellulin by osmotic minipumps for 7 days increased urine output by almost 100% in the rat (97). Intravenously infused EGF increased urine output and Na + excretion but had no effect on K + excretion in conscious sheep, suggesting that renal effect of EGF may be species-dependent (98,99). These variable results may result, at least in part, from opposite effects of EGF on transport in various tubular segments and on other processes affecting renal Na + handling, such as renal vascular tone or renin secretion.…”