Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats

Abstract

Impaired growth in utero predicts a low nephron number and high blood pressure later in life as does slowed or accelerated growth after a normal birth weight. We measured the effects of early postnatal growth restriction, with or without prenatal growth restriction, on blood pressure and nephron number in male rat offspring. Bilateral uterine artery and vein ligation were performed to induce uteroplacental insufficiency (Restricted) on day 18 of pregnancy. Postnatal growth restriction was induced in a subset of sham operated control animals by reducing the number of pups at birth to that of the Restricted group (Reduced Litter). Compared to Controls, Restricted pups were born smaller while Reduced Litter pups weighed less by postnatal day 3 and both groups remained lighter throughout lactation. By 10 weeks of age all animals were of similar weight but the Reduced Litter rats had elevated blood pressure. At 22 weeks, Restricted but not Reduced Litter offspring were smaller and the blood pressure was increased in both groups. Restricted and Reduced Litter groups had fewer glomeruli and greater left ventricular mass than Controls. These results suggest that restriction of both perinatal and early postnatal growth increase blood pressure in male offspring. This study also demonstrates that the early postnatal period is a critical time for nephron endowment in the rat.