In Utero Exposure to Fine Particulate Matter Causes Hypertension Due to Impaired Renal Dopamine D1 Receptor in Offspring

Zhengmeng Ye, Xi Lu, Yi Deng, Xinquan Wang, Shuo Zheng, Hongmei Ren, Miao Zhang, Tingting Chen, Pedro A. Jose, Jian Yang, Chunyu Zeng
2018 Cellular Physiology and Biochemistry  
Background/Aims: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM 2.5 ) exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D 1 receptor (D 1 R), regulated by G protein-coupled receptor kinase type 4 (GRK4), plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D 1 R dysfunction is involved in
more » ... on is involved in PM 2.5 -induced hypertension in the offspring. Methods: Pregnant Sprague-Dawley rats were given an oropharyngeal drip of PM 2.5 (1.0 mg/kg) at gestation day 8, 10, and 12. The blood pressure, 24-hour sodium excretion, and urine volume were measured in the offspring. The expression levels of GRK4 and D 1 R were determined by immunoblotting. The phosphorylation of D 1 R was investigated using immunoprecipitation. Plasma malondialdehyde and superoxide dismutase levels were also measured in the offspring. Results: As compared with saline-treated dams, offspring of PM 2.5 -treated dams had increased blood pressure, impaired sodium excretion, and reduced D 1 R-mediated natriuresis and diuresis, accompanied by decreased renal D 1 R expression and GRK4 expression. The impaired renal D 1 R function and increased GRK4 expression could be caused by increased reactive oxidative stress (ROS) induced by PM 2.5 exposure. Administration of tempol, a redox-cycling nitroxide, for 4 weeks Ye et al.: in Utero Exposure to Fine Particulate Matter and Hypertension in the offspring of PM 2.5 -treated dam normalized the decreased renal D 1 R expression and increased renal D 1 R phosphorylation and GRK4 expression. Furthermore, tempol normalized the increased renal expression of c-Myc, a transcription factor that regulates GRK4 expression. Conclusions: In utero exposure to PM 2.5 increases ROS and GRK4 expression, impairs D 1 Rmediated sodium excretion, and increases blood pressure in the offspring. These studies suggest that normalization of D 1 R function may be a target for the prevention and treatment of the hypertension in offspring of mothers exposed to PM 2.5 during pregnancy.
doi:10.1159/000488418 pmid:29614490 fatcat:kaqrgaulrzgebbs567ykcmjeym