We have previously observed that many of the renal and hemodynamic adaptations seen in normal pregnancy can be induced in virgin female rats by chronic systemic vasodilation. Fourteen-day vasodilation with sodium nitrite (NaNO2) or nifedipine (NIF) produced plasma volume expansion (PVE), hemodilution and increased renal medullary phosphodiesterase 5 A (PDE5A) protein. The present study examined the role of the RAAS in this mechanism. Virgin females were treated for 14 days with NIF; 10 mg/kg/day, NIF with spironolactone (SPR; mineralocorticoid receptor (MR) blocker, 200-300 mg/kg/day), NIF with losartan (LOS; AT1 receptor blocker, 20 mg/kg/day), enalapril (ENAL; ACE inhibitor, 62.5 mg/L), or vehicle (CON). Mean arterial pressure (MAP) was reduced 7.4±0.5% with NIF, 6.33±0.5% with NIF+SPR, 13.3±0.9% with NIF+LOS, and 12.0±0.4% with ENAL vs. baseline MAP. Compared to CON (3.6±0.3%), plasma volume factored for body weight was increased by NIF (5.2±0.4%) treatment but not by NIF+SPR (4.3±0.3%), NIF+LOS (3.6±0.1%), or ENAL (4.0±0.3%). NIF increased PDE5A protein abundance in the renal inner medulla and SPR did not prevent this increase (188±16% and 204±22% of CON respectively). NIF increased the α-subunit of the epithelial sodium channel (ENaC) protein in renal outer (365±44%) and inner medulla (526±83%), and SPR prevented these changes. There was no change in either PDE5A or ENaC abundance vs. CON in rats treated with NIF+LOS or ENAL. These data indicate that the PVE and renal medullary adaptations in response to chronic vasodilation result from RAAS signaling, with increases in PDE5A mediated through AT1R and ENaC through the MR.