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

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Abstract

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 D1receptor (D1R) isascribed to the pathogenesis of hypertension, which is associated with reactive oxidativestress (ROS). In this study, we test whether dysfunction of renal D1R 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 D1R expression, higher D1R phosphorylation, and D1R-mediated natriuresis and diuresis were lost. As an important kinase of D1R phosphorylation, G coupled receptor protein kinase 4 (GRK4) expression was increased in LPS rats. Tempol treatment reversed the decreased D1R expression, increased D1R phosphorylation and GRK4 expression. Moreover, the impaired D1R-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 D1R function, leads to hypertension in offspring. Reversion of renal D1R function by alleviation of ROS might be a target for therapy of fetal programming hypertension.

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