孕期免疫炎症刺激可引起子代（F1）血压升高。我们前期实验发现该效应可通过跨代遗传影响到F2代子鼠。F1、F2代子鼠均表现为基础状态下24小时尿钠排泄功能降低以及肾脏AT1R介导的尿钠潴留作用增强，提示AT1R功能增强可能是血压跨代遗传效应的重要原因。我们前期表明，GRK4可以正向调节AT1R功能, SHR大鼠随着血压升高GRK4启动子区甲基化程度降低， mRNA及蛋白表达升高，而我们发现F1、F2代子鼠肾脏GRK4 mRNA及蛋白表达水平均显著升高；当使用甲基化转移酶抑制剂后表达均显著恢复。 因此，我们推测GRK4启动子区去甲基化可能是F1、F2代子鼠肾脏GRK4 mRNA表达升高及AT1R介导的尿钠潴留作用增强的重要原因。该项目拟研究并证实孕期免疫炎症刺激可能通过GRK4表观遗传修饰调节AT1R功能进而导致连续子代血压跨代遗传效应，并为高血压的遗传机理提供新的认识。

Prenatal lipopolysaccharide (LPS) exposure results in increased blood pressure in F1 generation. Our preliminary result showed this effect could pass to F2 generation. Both the F1 and F2 generations showed decreased sodium excretion and increased renal AT1R-induced urinary sodium retention, indicating that the enhanced AT1R function may play an important role in the transgenerational genetic effects of blood pressure. Our previous studies showed that GRK4 could positively regulate AT1R function and protein expression, and the SHR showed decreased methylation in promoter of GRK4, and increased mRNA and protein expression, but reversed to normal after treatment of 5-azacitidine, a inhibitor of methylation transferase. We found that both of the F1 and F2 generations showed increased GRK4 mRNA and protein expression, but restored significantly after 5-azacitidine treatment. So, we presumed that demethylation of GRK4 promoter may play an important role in increased GRK4 mRNA level and enhanced AT1R-induced sodium retention in F1 and F2 generations. Our study will provide a new idea on genetic mechanism for hypertension.