Placental Insufficiency Leads to Development of Hypertension in Growth-Restricted Offspring

Abstract

Low birth weight is a suggested risk factor for the development of hypertension. The purpose of the present study was to determine whether a model of intrauterine growth restriction produced in response to placental insufficiency in the pregnant rat was associated with marked elevations in blood pressure. Reduced uterine perfusion initiated in late gestation resulted in low-birth-weight offspring (5.8+/-0.1 versus 6.6+/-0.2 g, P<0.05, growth-restricted versus control, respectively). Mean arterial pressure, as measured in conscious, chronically instrumented rats, was significantly elevated as early as 4 weeks of age (113+/-3 versus 98+/-2 mm Hg, P<0.05) and was associated with significant decreases in body weight (66+/-2 versus 81+/-3 g, P<0.05) in growth-restricted (n=15) versus control (n=15) rats. Marked elevations in arterial pressure at 8 weeks of age (male: 133+/-3 versus 121+/-6 mm Hg, P<0.05; female: 137+/-4 versus 112+/-6 mm Hg, P<0.01) were associated with sex-specific decreases in body weight (male: 251+/-6 versus 275+/-10 g, P<0.05; female: 163+/-6 versus 180+/-6 g) in male growth-restricted (n=12) versus male control (n=9) rats and in female growth-restricted (n=8) versus female control (n=7) rats. At 12 weeks of age, hypertensive (144+/-4 versus 131+/-3 mm Hg, P<0.05) male growth-restricted offspring (n=10) had no alterations in glomerular filtration rate (2.3+/-0.3 versus 2.2+/-0.2 mL/min) compared with control (n=10) offspring; even when adjusted for kidney weight (1.7+/-0.3 versus 1.5+/-0.3 mL x min(-1) x g(-1) kidney), despite marked decreases in body weight (305+/-9 versus 343+/-10 g, P<0.05). These data suggest that placental insufficiency induced by reduced uterine perfusion in the pregnant rat results in low-birth-weight offspring predisposed to development of hypertension.