Insulin-like growth factor I alters renal function and stimulates renin secretion in late gestation fetal sheep

1. While it is known that treatment with insulin-like growth factor I (IGF- I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of IGF-I on fetal renal function. To investigate the acute effects of IGF-I on fetal renal function and on the activity of t he fetal renin-angiotensin system, studies were carried out in 12 chronical ly catheterized fetal sheep aged 120 +/- 1 days, before and during a 4 h I. V. infusion of IGF-I at 80 mug h(-1). Seven control fetuses were infused ov er the same period with vehicle (0.1% bovine serum albumin in 0.15 M saline ). 2. IGF-I infusion increased plasma IGF-I concentrations by about 80%. There was a small fall in arterial P-O2 (P < 0.01), arterial P-CO2 increased (P < 0.05), plasma lactate levels increased (P < 0.01) and arterial pH fell (P < 0.05). Fractional bicarbonate reabsorption increased and bicarbonate exc retion decreased (P < 0.05). 3. Infusions of IGF-I had no sustained effect on fetal arterial pressure. G lomerular filtration rate (GFR) did not change significantly during IGF-I i nfusion, but renal blood flow (RBF) fell (P < 0.05). Therefore filtration f raction relative to control values increased (P < 0.05), suggesting that ef ferent arteriolar vasoconstriction had occurred. 4. ICP-I infusion led to an antidiuresis (P < 0.01), a rise in urinary osmo lality (P < 0.05) and a fall in free water clearance (P < 0.01). Since feta l P-O2 fell, it is probable that these effects a ere mediated by arginine v asopressin. 5. The excretion rates of sodium, chloride and phosphate were all reduced b y 4 h of infusion (P < 0.05), because their fractional reabsorption rates w ere all increased (sodium, P < 0.01; chloride, P < 0.01; and phosphate, P < 0.05). 6. Plasma renin concentration increased by 275 +/- 52% during infusion of I GF-I (P < 0.005). Plasma renin activity also increased (P < 0.005), while c irculating angiotensinogen concentrations fell (P < 0.05). 7. In the adult, IGF-I increases both RBF and GFR, enhances tubular reabsor ption and stimulates the renin-angiotensin system. In the fetus, however, i t decreased RBF and had no effect on GFR, but was associated with enhanced tubular function and intense stimulation of renin secretion. Some of these effects of IGF-I on fetal renal function may be involved in maturation of t he kidney in preparation for life after birth.