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Prenatal lipopolysaccharide exposure results in dysfunction of the renal dopamine D1 receptor in offspring.

Free radical biology & medicine (2014-09-23)
Xinquan Wang, Hao Luo, Caiyu Chen, Ken Chen, Jialiang Wang, Yue Cai, Shuo Zheng, Xiaoli Yang, Lin Zhou, Pedro A Jose, Chunyu Zeng
ABSTRACT

Adverse environment in early life can modulate the adult phenotype, including blood pressure. Lipopolysaccharide (LPS) exposure in utero results in increased blood pressure in the offspring, but the exact mechanisms are not clear. Studies have shown that the renal dopamine D1 receptor (D1R) plays an important role in maintaining sodium homeostasis and normal blood pressure; dysfunction of D1R is associated with oxidative stress and hypertension. In this study, we determined if dysfunction of the renal D1R is involved in fetal-programmed hypertension, and if oxidative stress contributes to this process. Pregnant Sprague-Dawley (SD) rats were intraperitoneally injected with LPS (0.79 mg/kg) or saline at gestation days 8, 10, and 12. As compared with saline-injected (control) dams, offspring of LPS-treated dams had increased blood pressure, decreased renal sodium excretion, and increased markers of oxidative stress. In addition, offspring of LPS-treated dams had decreased renal D1R expression, increased D1R phosphorylation, and G protein-coupled receptor kinase type 2 (GRK2) and type 4 (GRK4) protein expression, and impaired D1R-mediated natriuresis and diuresis. All of the findings in the offspring of LPS-treated dams were normalized after treatment with TEMPOL, an oxygen free radical scavenger. In conclusion, prenatal LPS exposure, via an increase in oxidative stress, impairs renal D1R function and leads to hypertension in the offspring. Normalization of renal D1R function by amelioration of oxidative stress may be a therapeutic target of fetal programming of hypertension.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Dopamine D1A Receptor Antibody, CT, cytoplasmic, Chemicon®, from rabbit
Sigma-Aldrich
Monoclonal Anti-ABCA1 antibody produced in mouse, clone 1H4, ascites fluid
Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O26:B6, ≥10,000 EU/mg, purified by phenol extraction
Sigma-Aldrich
Anti-ABCA1 antibody produced in rabbit, affinity isolated antibody