Abstract 218: Role of Thioredoxin 1 in the Impaired Renal Sodium Excretion in D5F173L Transgenic Mice

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 thioredoxin (Trx) 1 expression was lower, while Na+-K+-ATPase activity was higher in kidney from F173L mice and F173L transfected mouse proximal tubule epithelial cells (mRPT). Supplement with Trx1 could restore Na+-K+-ATPase activity in F173L transfected mRPT cells. Those results were confirmed in primary cultured mRPT cells from wild-type and 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. Introduction: D5 receptor mutant F173L has been found to be related with hypertension. To investigate the role of D5 receptor in the development of hypertension, we establish D5F173L transgenic mice. Our preliminary study found those mice develop hypertension with impaired sodium excretion. The previous studies reported that the hypertension of D5-/- mice was closely related with oxidative stress. To investigate the role of ROS in the impaired renal function in F173L mice, we selected some genes related oxidative stress and found the mRNA and protein expression of Trx1 were significantly decreased in the kidney of D5F173L transgenic mice. Result: We found that D5 mutant F173L increases blood pressure, via decreased Trx1 expression, decreased D5 receptor mediated renal sodium excretion, consequently leads to hypertension.