Objective To investigate the mechanism(s) of dopamine D_5 receptor regulation to hypertension involved in the antioxidant actions.Methods We investigated blood pressures in D_5 receptor deficient(D_5-/-) and wild type(D_5 / ) mice,and NADPH oxidase protein expression(p47~(phox)) and activity in kidney of those mice.We also checked super oxide and hydrogen peroxide production by using HEK-293 cells heterologously expressing human D_5 receptor.Result The systolic,diastolic and mean arterial blood pressures,and NADPH oxidase activity and p47~(phox) expression were higher in D_5-/-than D_5 / mice.In HEK-293 cells heterologously expressing human D_5 receptor,its agonist,fenoldopam,decreased super oxide and hydrogen peroxide production.Conclusion\ The ability of D_5 receptor stimulation to inhibit NADPH oxidase activity so as to decrease ROS production may explain,in part,the antihypertensive action of D_5 receptor activation.