Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep

In the adult, insulin-like growth factor I (IGF-I) increases glomerular fil tration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically cath eterized fetal sheep (120 +/- 1 days gestation) were infused intravenously for up to 10 days with 80 mug/h IGF-I (n = 5) or vehicle (0.1% BSA in salin e, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reab sorption increased (P< 0.05). However, by 4 days, GFR per kilogram had rise n by 35 +/- 13% (P< 0.05), whereas RBF remained unchanged. Tubular growth a nd maturation may have occurred, as proximal tubular sodium reabsorption in creased by similar to 35% (P<0.005). Therefore, despite a marked increase i n filtered sodium (<similar to>30%, P< 0.05), fractional sodium reabsorptio n did not change. Although the effects of IGF-I on renal function were dela yed, plasma renin activity and concentration were both elevated after 4 h a nd remained high at 4 days (P< 0.05). Despite this, arterial pressure and h eart rate did not change. Kidneys of IGF-Iinfused fetuses weighed similar t o 30% more (P = 0.05) and contained similar to 75% more renin than control fetuses (P< 0.005). Thus, in the fetus, the renal effects of long-term IGF- I infusion are very different from the adult, possibly because IGF-I stimul ated kidney growth.