ASSA14-03-07 Prenatal Lipopolysaccharide Exposure Results in Dysfunction of Renal Dopamine D1 Receptor in Offspring Rats

Objective Adverse environmental exposure inuteropredisposes to adult disease, including hypertension. Exposure to lipopolysaccharide (LPS) results in increased blood pressure in offspring, but the exact mechanisms are not clear. Our previous study shows dysfunction of renal D 1 receptor (D 1 R) isascribed to the pathogenesis of hypertension, which is associated with reactive oxidativestress (ROS). In this study, we test whether dysfunction of renal D 1 R is involved in fetal programmed hypertension, and whether oxidative stress contribute to this process. Methods Pregnant Sprague–Dawley (SD) rats were intraperitoneally injected with LPS (0.79 mg/kg) or saline (0.5 ml) at gestation day 8, 10 and 12. After birth, the blood pressure is measured, and treated with or without antioxidant tempol in tap water for 3 weeks at postnatal 12 week. Results As compared with control rats, the LPS-treated offspring rats showed higher blood pressure, decreased renal sodium excretion with increased plasma ROS activity. After treatment with tempol for 3 week, the increased blood pressure, decreased sodium excretion were reversed to normal levels in LPS rats. Our further study found LPS rats had lower renal D 1 R expression, higher D 1 R phosphorylation, and D 1 R-mediated natriuresis and diuresis were lost. As an important kinase of D 1 R phosphorylation, G coupled receptor protein kinase 4 (GRK4) expression was increased in LPS rats. Tempol treatment reversed the decreased D 1 R expression, increased D 1 R phosphorylation and GRK4 expression. Moreover, the impaired D 1 R-mediated natriuresis and diuresis were restored to the control levels in LPS rats after tempol treatment. Conclusion Pprenatal LPS exposure, via impairment of ROS on renal D 1 R function, leads to hypertension in offspring. Reversion of renal D 1 R function by alleviation of ROS might be a target for therapy of fetal programming hypertension.