Hormonal, fluid, and electrolyte responses of sheep during chronic intravenous infusion of epidermal growth factor

Abstract

Epidermal growth factor (EGF) has been shown to increase water intake and urine volume. To further characterize these responses the effects of EGF on fluid balance, electrolyte, and hormone profiles were examined. After an 8-day control period, ewes received intravenous EGF at doses of 0 (n = 6), 2 (low dose, n = 6), 10 (medium dose, n = 6), or 20 micrograms/h (high dose, n = 5) for 4 days. During EGF treatment, water intake and urine volume increased (both P < 0.001) in a dose-related fashion, although fluid balance was unaffected. Feed intake and fecal dry matter output were reduced (both P < 0.001) by the two higher doses of EGF. EGF had no effect on plasma potassium, sodium, or osmolality, but there was a dose-related natriuresis (P < 0.001). Treatment with EGF increased plasma renin activity and aldosterone in the medium and high dose groups (both P < 0.001). Thus chronic intravenous infusion of 10-20 micrograms EGF/h into sheep caused polydipsia, polyuria, and natriuresis with neutral fluid balance. Whether the resultant polydipsia or polyuria was the primary response to EGF remains unclear.

Long-Term EGF Treatment Partially Prevents Reduction of Renal Blood Flow in Response to Neonatally Induced Partial Unilateral Ureteral Obstruction

“…EGF is both synthesized by cells in the thick ascending limbs of Henle’s loops and in the early part of the distal convoluted tubules [19]. Specific receptors for EGF in whole-kidney homogenates are well described [4] and the presence of EGF receptors has been demonstrated in the nephron [23]. …”

“…Thus, intravenous infusion of EGF into lactating ewes stimulated urine volume increase by 29–134%, and this effect was dose-related [31]. In ewes, the polyuria was found to occur on the first day of EGF infusion [23, 31]. The mechanism behind the EGF-induced polyuria, however, has not been fully elucidated [27].…”

Epidermal growth factor as a diuretic in sheep.

“…Lastly, i.v. infusion of low doses of EGF into early-lactating (Gow & Moore, 1992), anoestrous (Gow, Wilkinson, Silvapulle & Moore, 1992) and ovariectomized (Gow, Phillips, Chandler & Moore, 1993) ewes was shown to stimulate profound increases in water intake and urine volume and increased the urinary excretion of sodium (Gow et al 1992(Gow et al , 1993. In these studies, all animals had access to an ad libitum supply of water and thus could maintain normal fluid balance.…”

“…The doses of EGF which have been previously reported to stimulate profound increases in water intake and urine volume in sheep include 0 5 mg day' (Gow & Moore, 1992), 5 or 10 ,sg (kg live weight)' day' (Gow et at. 1992) and 10 or 20 jcsg h1 (Gow et al 1993). The dose of EGF chosen in the present experiment was 10 jug h' reported by us (Gow et at.…”

“…1992) and 10 or 20 jcsg h1 (Gow et al 1993). The dose of EGF chosen in the present experiment was 10 jug h' reported by us (Gow et at. 1993) to be diuretic, polydipsic and natriuretic in sheep.…”