title: Prenatal lipopolysaccharide exposure results in dysfunction of the renal dopamine D1 receptor in offspring.
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.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China. Electronic address: zhoulin@mail.tmmu.com.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China. Electronic address: chunyuzeng01@163.com.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D054771:G-Protein-Coupled Receptor Kinase 4 / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy; D015151:Immunoblotting; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D009318:Natriuresis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D017447:Receptors, Dopamine D1; D013113:Spin Labels; D011493:Protein Kinase C; C496569:Grk2 protein, rat; D054769:G-Protein-Coupled Receptor Kinase 2; D054771:G-Protein-Coupled Receptor Kinase 4; C517854:Grk4 protein, rat; C001803:tempol
keywords: D(1) dopamine receptor; Fetal programming; G protein-coupled receptor kinase; Hypertension; Lipopolysaccharide; Oxidative stress; TEMPOL