Dopamine receptor plays an important role in hypertension by regulation of sodium excretion.Disruption of the D5 receptor results in hypertension with increased activity of the sympathetic nervous system.D5 receptor mutant F173L has been found to be related with hypertension.To investigate the role of F173L in hypertension, we established F173L transgenic mice, it resulted that, as compared with wild-type mice, the blood pressure was higher, basal levels of sodium excretion was lower, and fenoldopam, a D1-like receptor agonist, mediated natriuresis and diuresis were impaired in F173L mice.Our further study found ROS might be involved in the hypertension of F173L mice, because ROS levels were higher in F173L, treatment of F173L with tempol reduced the ROS, lower the blood pressure and normalized the sodium excretion in F173L mice.Screening studies found Trx1 expression was lower, while Na+-K+-ATPase activity was higher in kidney from F173L mice and F173L transfected mRPT cells.Supplement with Trx1 could restore Na+-K+-ATPase activity in F173L cells.Those results were confirmed in primary cultured RPT cells from wild-type D5F173L transgenic mice.We conclude that D5 mutant increases blood pressure, possibly via decreased D5 receptor mediated sodium excretion by decreased Trx1 expression in kidney.