This study aimed to verify the effects of an acute increase in blood pressure (BP) and/or renal sympathetic nerve activity (rSNA) on the renal excretion of sodium and water and its potential effect on the regulation of NHE3 activity. Uninephectomized anesthetized male Wistar rats were divided into three experimental groups: 1) Sham, the rats had their BP and rSNA recorded, and urine was collected for 2 h; 2) bicuculline (Bic) paraventricular nucleus of the hypothalamus (PVN), rat BP, and rSNA were recorded, and urine was collected for 1 h at baseline conditions and 1 h after bicuculline injection into the PVN; 3) RNS + Bicuculine injection into the PVN, BP, and rSNA were recorded, and urine was collected 1h after RNS and 1 h after bicuculline injection into the PVN. Renal nerve stimulation (RNS) decreased sodium and water excretion independent of changes in BP. However, after Bic in the PVN during RNS stimulation, BP and rSNA increased up to 30% and 60%, respectively, increasing diuresis (5-fold) and natriuresis (2.3-fold), accompanied by a significant reduction in the NHE3 activity independent of GFR changes. In conclusion, an acute increase in BP overcomes such effects, generating diuresis, natriuresis, and NHE3 activity inhibition.