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 filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 +/- 1 days gestation) were infused intravenously for up to 10 days with 80 microgram/h IGF-I (n = 5) or vehicle (0.1% BSA in saline, 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 reabsorption increased (P < 0.05). However, by 4 days, GFR per kilogram had risen by 35 +/- 13% (P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ~35% (P < 0.005). Therefore, despite a marked increase in filtered sodium (~30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days (P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-I-infused fetuses weighed ~30% more (P = 0.05) and contained ~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 stimulated kidney growth.
Marsh
A C
AC
School of Physiology and Pharmacology, The University of New South Wales, Sydney, New South Wales 2052.
Gibson
K J
KJ
Wu
J
J
Owens
P C
PC
Owens
J A
JA
Lumbers
E R
ER
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000196:embryology* / Q000378:metabolism / Q000502:physiology*; D009929:Organ Size; D011247:Pregnancy; D012083:Renin / Q000096:biosynthesis* / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012756:Sheep
D007334:Insulin-Like Growth Factor I; D012083:Renin