Some populations ingesting low protein-high salt diets show a high incidence of end stage renal failure due to glomerulonephritis, diabetes, and hypertension. This proposal focuses on the role of maternal dietary protein and salt on progeny susceptibility to cardiovascular injury induced by renal ablation. The overall hypothesis postulates that the variability to renal injury and uremic death in an individual could be modified by the levels of maternal dietary protein and salt during perinatal life. Specifically, maternal environment changes the intrinsic characteristics of the offspring kidney by affecting, among other things, early blood pressure and renal development. After weaning, offspring on normal diets maintain normal blood pressure and renal function. However, this is achieved by adaptive mechanisms that alter renal reserve.Therefore, the kidney's response to injury and stress (decrease in renal mass, diabetes, diets, toxics, inflammation etc.) result in diverse blood pressure and renal patterns of damage. The capacity of the glomerulus to increase filtration by enlarging filtering surface area is pivotal for the maintenance of filtration without glomerular hypertension. It is postulated that this capacity is modified by maternal environment. This hypothesis will be tested in Sprague-Dawley rats by using a balanced multifactorial randomized design and statistically assessed by multivariate analysis techniques. The dietary factors will be protein (low; 11% high: 40% and normal: 23%) and NaCl (low: 0.3%, high:4% and normal:0.6%) to be given to the mother during pre-pregnancy, pregnancy, and lactation in 9 protein-salt dietary combinations. After weaning pups will receive a normal diet. At eight weeks of age when pups are sexually mature, pups will be randomly assigned to have 1-2/3 nephrectomies or sham operations (18 groups). Offspring will be monitored to determine morbidity (blood pressure, proteinuria, renal structure) and mortality. Subset of offspring will be randomly allocated for studies to be done as sucklings (day 0-1,7 and 19) and at postweaning age (70 days). The blood pressure response to maternal dietary manipulation and renal ablation will be continuously monitored using telemetry technology from renal ablation to death. Renal reserve will be tested by acute protein load. Filtration surface will be determined by single nephron studies. The critical end points to test the hypothesis will be: 1) glomerular maturation, number, tabular and vascular mass in sucklings, 2) glomerular number, tubular, vascular mass and histopathology of shams and remnant kidneys, 3) total blood pressure response in mmHg/entire period of renal ablation, 4) proteinuria, whole kidney function, and reserve in weanling and mature offspring and 5) glomerular hemodynamics in sham and remnant kidneys. If proven, this work will help the understanding of the variability in hypertension and renal damage in renal disease, establish rationale for preventive measurements, and most important, this work will emphasize the role of maternal nutrition as an essential factor in the health of society.
