Maternal low protein diet: Developmental origin of adult hypertension

Abstract

ObjectiveWe hypothesized that maternal isocaloric, low‐protein, diet during pregnancy programs the Renin Angiotensin System in the fetus leading to hypertension in the adult. We conducted studies on pregnant mice, on isocaloric, normal or low protein diet (50% and 33% less protein).MethodsProteins and mRNA levels were measured using western blot and real time PCR technique and blood pressure was recorded by the non‐invasive tail cuff system.ResultsMaternal low protein diet (MLPD) resulted in low birth weight and rapid catch up growth in both male and female offspring. MLPD induced hypertension in female mice offspring at 11 weeks of age, whereas no hypertension was observed in male offspring by 20th week of age. Our results indicate increased AGT and ACE, but decreased AT2, expression of mRNA, with no change in the protein expression of AGT but decreased protein expression of both, ACE and AT2 receptors with MLPD. Promoter methylation analysis of ACE gene showed hypo‐methylation of the CpG islands as a consequence of maternal protein deprivation.ConclusionsOur studies establish that MLPD programs hypertension in female offspring by epigenetic programming of the renin‐angiotensin system.