55 Is Nephron Number Reduction Sufficient to Explain the Fetal Programming of Hypertension

Abstract

Introduction: Intrauterine growth restriction (IUGR) is associated with increased risk of cardiovascular and metabolic diseases in adulthood. Nephron number reduction has been proposed as a key mechanism for later hypertension. Aim: To compare the long term effects of two models of IUGR on arterial systolic blood pressure (SBP) and renal function in adult rats. Methods: 3 groups of animals were investigated: group I, controls: offspring of dams fed normal diet (NP, casein 22 %); group II: offspring of dams fed isocaloric low-protein diet (LP, casein 9 %); group III: offspring of dams that received 3 daily intramuscular injections of betamethasone (0.25 mg/kg) on gestational days 17,18, 19 (BET). SBP, glomerular number, and renal function were obtained in 12 months old animals. Results: (mean +/- SEM). Glomerular number was significantly reduced in IUGR rats (38 % in LP rats and 50 % in BET rats vs. controls p<0.05). At 2 months, unlike BET rats, LP rats displayed a significant elevated SBP compared to controls (135 +/- 3, 144 +/- 3, 130 +/- 3 mmHg in groups BET, LP, controls; p<0.05). At 12 months, SBP levels were not significantly different between the groups despite an alteration of Creatinine Clearance in BET rats (3.25 +/-0.2, 4.82 +/-0.4, 4.88+/-0.5, ml/min/kg in groups BET, LP and controls; p<0.05). Conclusion: Despite no differences in birth weight, maternal low protein diet and short course maternal injections of betamethasone have different effects on SBP, renal function and GT in adult rats, while both reduce nephron number. The hypothesis of an inborn nephron deficit associated with single nephron hyperfiltration appears not sufficient to explain the fetal programming of hypertension.