Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor

Abstract

The infusion of low doses of epidermal growth factor (EGF) into lactating ewes stimulates water intake and urine volume. The plasma concentrations and daily output of various electrolytes in milk and urine are also affected. We have investigated this further by recording the effects of EGF infusion on fluid balance, electrolyte profiles and plasma concentrations of glucose and parathyroid hormone (PTH) in non-pregnant, non-lactating ewes. Twenty-four animals (n = 8 per group) received infusions of 100 ml saline/day into the jugular vein for 10 days (days 1-10) followed by EGF at a dose rate of either 1 (low dose), 5 (medium dose) or 10 (high dose) micrograms/kg liveweight per day in 100 ml saline for 5 days (days 11-15). All ewes then received an infusion of 100 ml saline/day for 10 days (days 16-25). Most plasma and urine samples had undetectable concentrations of EGF-immunoreactive material during the periods of saline infusion. During EGF infusion, the highest amounts of EGF infusate excreted in urine were 1.6, 5.9 and 5.6% for ewes in low, medium and high dose groups respectively. Water intake increased by 17% (0.5 kg), 88% (2.5 kg) and 89% (2.3 kg) and urine volume increased by 29% (0.5 kg), 108% (2.2 kg) and 134% (2.1 kg) for the three groups respectively. Fluid balance and feed intake were not affected by EGF infusion, but the output of faecal dry matter was reduced in ewes receiving the two higher doses of EGF. All levels of EGF resulted in hypocalcaemia, increased plasma PTH concentrations and hypermagnesaemia. There was no effect of EGF on plasma concentrations of K+ and glucose or on daily urinary excretion of K+ and Mg2+. The only response to the low dose was a reduced plasma concentration of Na+ and an increased daily urinary urate excretion. The two higher doses increased the daily urinary excretion of Na+, PO4(3-) and urate, but had no effect on the respective concentrations in plasma. Urinary Ca2+ excretion was reduced only during infusion of the medium dose of EGF. The responses of most variables were similar during infusion of the medium and high doses of EGF. All three doses of EGF induced polydipsic and diuretic responses in ewes, and infusions of 5-10 micrograms EGF/kg liveweight per day affected renal excretion of Ca2+, Na+ and PO4(3-). We interpret the responses of the kidney and plasma PTH concentrations as a means of maintaining the homeostasis of plasma profiles of electrolytes.

The role of the EGF family of ligands and receptors in renal development, physiology and pathophysiology

“…Renal artery infusion of EGF in sheep produced natriuresis and diuresis, suggesting a tubular effect [25]. When administered basolaterally to isolated rabbit cortical collecting duct, EGF inhibited sodium transport by inhibiting the epithelial sodium channel (ENaC) [26, 27], and also inhibited the hydroosmotic effect of vasopressin [28].…”

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

“…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].…”

“…The mechanism behind the EGF-induced polyuria, however, has not been fully elucidated [27]. Previously, it has been found that active sodium reabsorption in perfused isolated rabbit cortical collecting ducts are inhibited by EGF and that EGF can regulate membrane transport events in vitro [31]. Sack and Talor [32] already in 1988 suggested a physiological role for EGF in the proximal tubules and medullary portions of the rabbit nephron, due to the presence of low- and high-affinity binding sites for EGF.…”

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.…”

“…On the other hand, if EGF acted directly on the kidney, resulting in polyuria (with secondary polydipsia), water restriction would result in progressive dehydration. 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).…”