Intergenerational programming of impaired nephrogenesis and hypertension in rats following maternal protein restriction during pregnancy

Associations between birth weight and CVD in adult life are supported by experiments showing that undernutrition in fetal life programmes blood pressure. In rats, the feeding of a maternal low-protein (MLP) diet during gestation programmes hypertension. The present study aimed to assess the potential for a nutritional insult to impact across several generations. Pregnant female Wistar (F-0) rats were fed a control (CON; n 10) or MLP (n 10) diet throughout gestation. At delivery all animals were fed a standard laboratory chow diet. At 10 weeks of age, F-1 generation offspring were mated to produce a second generation (F-2) without any further dietary change. The same procedure produced an F-3 generation. Blood pressure in all generations was determined at 4, 6 and 8 weeks of age and nephron number was determined at 10 weeks of age. F-1 generation MLP-exposed offspring exhibited raised (P<0.001) systolic blood pressure (male 143 (SEM 4) mmHg; female 141 (SEM 4) mmHg) compared with CON animals (male 132 (SEM 3) mmHg; female 134 (SEM 4) mmHg). Raised blood pressure and reduced nephron number was also noted in the F-2 generation (P<0.001) and this intergenerational transmission occurred via both the maternal and paternal lines, as all three possible offspring crosses (NILP X CON, CON X MLP and MLP X MLP) were hypertensive (132 (SEM 3) mmHg) compared with CON animals (CON X CON; 123 (SEM 2) mmHg). No effect was noted in the F-3 generation. It is concluded that fetal protein restriction may play a critical role in determining blood pressure and overall disease risk in a subsequent generation.