High sodium intake increases blood pressure and alters renal function in intrauterine growth-retarded rats.

A suboptimal fetal environment increases the risk to develop cardiovascular disease in the adult. We reported previously that intrauterine stress in response to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and compromises renal development, leading to an altered renal function in the adult offspring. Here we tested the hypothesis that high dietary sodium intake in rats with impaired renal development attributable to intrauterine stress, results in increased blood pressure, altered renal function, and organ damage. In rats, intrauterine stress was induced by bilateral ligation of the uterine arteries at day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium drinking water (2% sodium chloride). At the age of 16 weeks, rats were instrumented for monitoring of blood pressure and renal function. After intrauterine stress, litter size and birth weight were reduced, whereas hematocrit at birth was increased. Renal blood flow, glomerular filtration rate, and the glomerular filtration fraction were increased significantly after intrauterine stress. High sodium intake did not change renal function and blood pressure in control animals. However, during high sodium intake in intrauterine stress offspring, renal blood flow, glomerular filtration rate, and the filtration fraction were decreased, and blood pressure was increased. In addition, these animals developed severe albuminuria, an important sign of renal dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal development, results in sodium-dependent hypertension and albuminuria.

Reduced uteroplacental blood flow alters renal arterial reactivity and glomerular properties in the rat offspring.

Fetal malnutrition and hypoxia may modify organ system maturation and result in cardiovascular diseases in the adult. We tested whether intrauterine stress (IUS) leads to persistent alterations of renal biology. In rats, intrauterine stress was induced by ligation of the uterine arteries at day 17 of pregnancy. Renal arteries of the 21-day-old male offspring were isolated to study pharmacological reactivity. Kidneys were dissected to analyze renal structure and beta-adrenoceptor expression. At 21 days of age, half of the animals underwent unilateral left nephrectomy. At the age of 12 weeks, rats were instrumented for blood pressure monitoring, blood sampling, and renal function measurements. After IUS, litter size and birth weight were reduced, whereas the hematocrit was increased. Renal arterial responses to beta-adrenergic stimulation and sensitivity to adenylyl cyclase activation were increased, along with the renal expression of beta2-adrenoceptors. At 21 days and at 6 months of age, the number and density of the glomeruli were reduced, whereas their size was increased. The filtration fraction and urinary albumin concentration were increased 12 weeks after intrauterine stress. In control rats, removal of the left kidney at 21 days of age did not affect kidney function and blood pressure. However, after IUS, the remaining right kidney failed to compensate for the loss of the left kidney, and blood pressure was increased. In conclusion, prenatal stress transiently modifies renal arterial reactivity and results in long-lasting adverse effects on renal structure and function and on renal compensatory mechanisms.