These studies will investigate the effects of genetics, maternal environment and maternal dietary salt excess, on BP development in offspring of genetically hypertensive rats, postulating that: the development and severity of hypertension in a susceptible adult individual could be modified by salt excess acting during prenatal and early postnatal life. Salt excess during pregnancy by altering maternal environment accelerates the in-utero development of offspring hypertension. If salt excess persists, the lactating mother transmits to the offspring, via milk, a factor(s) transported through the gastrointestinal tract which in combination to abnormal renal development induces changes in body fluids, BP, and the kidney leading to further acceleration and or aggravation of offspring hypertension. After weaning, salt intake and other environmental factors associated with the offspring's new stages of life modulate the final course of BP development through maturity. To test this hypothesis we will use an embryo transfer and cross-suckling approach and multivariate analysis. The spontaneously hypertensive rat (SHR) and the control Wistar-Kyoto rat (WKY) will be used; the environmental factor will be NaC1 in the diet of recipient mother, nurse and weanling. The diet salt content (low 0.3% or 4% salt diets given after and maintained on their assigned diets until delivery. Then one """"""""environmental"""""""" and one """"""""genetic"""""""" manipulation will be done. Each mother will be a nurse and her diet will be randomly assigned to either low or high salt (16 groups). Half the male pups of each strain will then be cross-suckled (32 groups). All pups will be weaned at 19 days, and the pup's diet randomized to high or low salt (64 groups). Maternal endpoints will be: pre-natal body weigh;t, BP, heart rate (days 15, 18, and 20 post-mating). Offspring endpoints will be fetal (days 15, 18 and 20) and suckling (days 0, 7 and 19) BP, heart rate, kidney/body weight ratio and morphologic renal development. Post-weaned offspring will have BP measurements at 6, 16 weeks, 6, 9, 12 months. Micropuncture will be used to measure in-utero and early post-natal BP. The proposed studies will allow to differentiate the role of genetic, maternal environment and extrinsic environment in the development of hypertension, which will provide a rational for preventative measures in the hypertension prone individual.
| Lee, Jong Y; Azar, Silvia H (2010) Wistar-Kyoto and spontaneously hypertensive rat blood pressure after embryo transfer into different wombs and cross-suckling. Exp Biol Med (Maywood) 235:1375-84 |
| Azar, S H; Hensleigh, H C; Matthys, E et al. (1991) Oviductal-uterine and nursing environment alter blood pressure development in spontaneously hypertensive and normotensive rats. J Hypertens Suppl 9:S294-5 |
| Azar, S; Kabat, V; Bingham, C (1991) Environmental factor(s) during suckling exert long-term effects upon blood pressure and body weight in spontaneously hypertensive and normotensive rats. J Hypertens 9:309-27 |
| Azar, S; Meyer, M W; Myers, J (1986) Umbilical blood pressures and utero-placental blood flow in spontaneously hypertensive rats. J Hypertens Suppl 4:S369-71 |
