Low birth weight is associated with reduced nephron number and increased blood pressure in adulthood in a novel spontaneous intrauterine growth-restricted model in Yucatan miniature Swine

Abstract

Background: Impaired fetal growth and rapid postnatal growth are associated with programming of hypertension and metabolic syndrome in adulthood.

Objectives: This study evaluated this phenomenon in a novel spontaneous intrauterine growth-restricted (IUGR) model in Yucatan miniature pigs.

Methods: IUGR piglets (n = 6, 3 days old, 0.73 ± 0.11 kg) were paired with a normal weight (NW) same-sex littermate (n = 6, 1.11 ± 0.13 kg), fed milk replacer for 4 weeks followed by a standard diet ad libitum for 5 h/day. At 9 months of age, arterial blood pressure (BP) telemeters were implanted to assess BP before (0.5% NaCl) and after (4.5% NaCl) a 7-day salt-loading period. At 10 months of age, nephron numbers were determined.

Results: Prior to sexual maturity, IUGR pigs showed greater (p < 0.05) relative feed intake and experienced significant catch-up growth. Adult IUGR pigs also had higher BP (diastolic BP: 93.8 ± 5.5 vs. 90.0 ± 8.7 mm Hg, p < 0.05) and 43% fewer nephrons per kidney (p < 0.05). Nephron number was positively associated with birth weight and negatively correlated with BP (p < 0.05). Acute salt loading increased BP in both groups (p < 0.05); however, the degree of salt sensitivity was similar between groups (p > 0.05).

Conclusions: In conclusion, IUGR piglets have reduced nephron endowment associated with a modest BP increase in early adulthood. This new model can be used to conduct longitudinal mechanistic studies on the early programming phenomenon.