Renal Development and Blood Pressure in Offspring from Dams Submitted to High-Sodium Intake during Pregnancy and Lactation.

Exposure to an adverse environment in utero appears to programme physiology and metabolism permanently, with long-term consequences for health of the fetus or offspring. It was observed that the offspring from dams submitted to high-sodium intake during pregnancy present disturbances in renal development and in blood pressure. These alterations were associated with lower plasma levels of angiotensin II (AII) and changes in renal AII receptor I (AT(1)) and mitogen-activated protein kinase (MAPK) expressions during post natal kidney development. Clinical and experimental evidence show that the renin-angiotensin system (RAS) participates in renal development. Many effects of AII are mediated through MAPK pathways. Extracellular signal-regulated protein kinases (ERKs) play a pivotal role in cellular proliferation and differentiation. In conclusion, high-sodium intake during pregnancy and lactation can provoke disturbances in renal development in offspring leading to functional and structural alterations that persist in adult life. These changes can be related at least in part with the decrease in RAS activity considering that this system has an important role in renal development.

Inhibition of nuclear factor-kappa B activation reduces glycerol-induced renal injury.

BACKGROUND: Glycerol injection induces acute tubular necrosis that can progress to interstitial fibrosis. The oxidative stress seen in glycerol-treated animals can activate the nuclear factor kappa B (NF-kappa B) system. The aim of this study was to investigate the expression of NF-kappa B and mitogen-activated protein kinases (MAPKs) in the renal cortex and to determine its relationship with structural and functional renal changes in rats treated with glycerol or glycerol plus pyrrolidine dithiocarbamate (PDTC), a nonspecific NF-kappa B inhibitor with antioxidant properties. METHODS: Male Wistar rats were injected intramuscularly with 8 ml/kg of either 50% glycerol (n=22), glycerol+PDTC (n=25) or 0.15 M saline (n=10). The rats were killed, and the kidneys removed at 5 or 30 days after injection. mmunohistochemical results were scored according to the extent of staining. Interstitial lesions were evaluated through morphometry. Lipid peroxidation was estimated by measuring malondialdehyde in urine samples from control rats and glycerol-injected rats. RESULTS: By postinjection day 5, glycerol-only treated rats presented transitory increases in plasma creatinine levels, as well as in fractional excretion of sodium and potassium (p<0.001), which were attenuated in glycerol+PDTC treated rats (p<0.05). Cortical expression of macrophages and NF-kappa B was greater in glycerol-treated rats than in controls (p<0.001). Glycerol-induced histological nd immunohistochemical changes were attenuated by the addition of PDTC (p<0.001), which also reduced the glycerol-induced increase in urinary malondialdehyde (MDA) levels (p<0.05). CONCLUSIONS: We conclude that PDTC attenuates glycerol-induced renal injury by reducing NF-kappa B expression and decreasing lipid peroxidation in the renal cortex.

Postnatal renal development of rats from mothers that received increased sodium intake.

The newborn rat kidney is not fully developed until approximately 12 days after birth. Several lines of evidence suggest that angiotensin II (AII) participates in the postnatal development of the kidney. The aim of the present study was to analyze proliferating cell nuclear antigen (PCNA), fibronectin, alpha-smooth muscle-actin (alpha-SM-actin), and AII expression in renal cortex during development in rats born to mothers that received a normal (control) or increased (experimental) sodium intake during pregnancy. Ninety Wistar rats aged 1, 7, 15, and 30 days from the control and experimental groups were killed and the kidneys removed for histological and immunohistochemical studies. The results showed higher fibronectin, alpha-SM-actin, PCNA, and AII expression in the glomerular and tubulointerstitial areas of the renal cortex of 1- and 7-day-old animals, which decreased with renal development. The animals from the experimental group showed at 1 day of age a decrease in alpha-SM-actin, fibronectin, PCNA, and AII expression compared with controls of the same age ( P<0.05). In conclusion, our data show that increased sodium intake during pregnancy induces a reduction of alpha-SM-actin, fibronectin, and PCNA expression in the renal cortex tubulointerstitium and glomeruli of neonatal rats. These alterations may be related to the decrease of AII expression also observed in the renal cortex from these animals.