肾脏D1/D3多巴胺受体抑制尿钠吸收，AT1受体促进尿钠吸收，二者功能平衡在维持正常血压方面发挥重要作用；高血压状态下AT1受体功能增强，D1/D3受体功能减弱，但发生该失衡的原因尚不清楚。我们发现高血压时GRK4 A142V通过增强GRK4活性、削弱D1受体、增强AT1受体功能，但用D1受体拮抗剂肾脏灌注并不能完全阻断AT1受体的保钠潴水作用，说明还存在其它AT1受体制约因素。由于D1、D3受体之间具有协同作用，刺激D3受体可抑制AT1受体的表达；因为GRK4 A142V转基因小鼠肾脏在AT1受体功能增强的同时D3受体功能也降低，我们推测D3、D1受体之间具有协同抑制AT1受体作用，GRK4可能通过同时削弱D1、D3受体的表达和功能、间接增强AT1受体的功能。该问题的解决将有助于揭示高血压肾脏D1/D3受体与AT1受体功能失衡的原因，为寻找有效的高血压防治策略提供理论基础。

Renal D1/D3 dopamine receptors inhibit the urine sodium absorption, while AT1 receptors promote the sodium absorption. The functional balance between D1/D3 and AT1 receptors play a crucial role in blood pressure regulation. The function of AT1 receptor was amplified while that of D1/D3 was attenuated in hypertension, but factors contribute to this disbalance remains unclear.We previously found that during hypertension GRK4 A142V enhance AT1 receptor by by stimulating the GRK4 activity and impairing D1 receptor function, but D1 antagonist can not blocked the sodium-water reserving effect of AT1, indicating a possibility of other factors repressing AT1 fucntion. Since there is a synergetic effect between D1 and D3 receptors, stimulation of D3 can repress AT1 expression; GRK142V transgenetic mice exihibite a impaired renal D3 fucntion. Thus we propose that D1/ D3 receptors inhibit AT1 function synergetically, and that GRK4 strenthens the AT1 fucntion indirectly by abating D1/D3 expression and function. This project, based on our previous findings, aims to uncover the causes of the functional disbalance between D1/D3 and AT1 receptors in renal system in hypertension, in favor of the theoretical development for the prevention and treatment of hypertension.