We have demonstrated that oral contraceptive (OC) users exhibit elevated Angiotensin (Ang) II levels and Ang II type 1 receptor (AT1R) expression, indicative of renin angiotensin system (RAS) activation, yet the renal and systemic consequences are minimal, suggesting that there is increased vasodilatory activity, counteracting the effect of RAS activation. We hypothesized that the (nitric oxide) NO system would be upregulated in OC users and that this would be reflected by a blunted hemodynamic response to L-arginine infusion. All subjects were studied after a 7-day controlled sodium and protein diet. Inulin and paraminohippurate clearance techniques were used to assess renal function. L-arginine was infused at 100, 250 and 500 mg/kg, each over 30 minutes. Skin eNOS mRNA expression was assessed by real time PCR. While OC non-users exhibited significant increases in effective renal plasma flow (670.8±35.6 to 816.2±59.7 ml/min/1.73 m²) and glomerular filtration rate (133.4±4.3 to 151.0±5.7 ml/min/1.73m², p=0.04) and declines in renal vascular resistance (81.1±6.1 to 63.5±6.2 mmHg/ml/min, p=0.001) at the lower L-arginine infusion rates, the responses in OC users were blunted. While L-arginine reduced MAP at the 250 and 500 mg/kg doses in OC non-users, OC users only exhibited a decrease in MAP at the highest infusion rate. In contrast, tissue eNOS mRNA levels were higher in the OC users (p=0.04). In summary, theses findings suggest that the NO system is upregulated by OC use in young healthy women. Increased activity of the NO pathway may modulate the hemodynamic effects of RAS activation in OC users.