Renal blood flow (RBF) autoregulation is mediated by at least two mechanisms, the fast acting myogenic response (~5 s) and slow acting tubuloglomerular feedback (TGF, ~25 s). Previous studies suggest Epithelial Na⁺ Channel (ENaC) family proteins, ENaC in particular, mediate myogenic constriction in isolated renal interlobar arteries. However, it is unknown if ENaC mediated myogenic constriction contributes to RBF autoregulation in vivo. Therefore, the goal of this investigation was to determine if the myogenic mediated RBF autoregulation is inhibited in a mouse model of reduced ENaC (m/m). To address this goal, we evaluated the temporal response of RBF and renal vascular resistance (RVR) to a 2-minute step increase in mean arterial pressure (MAP). Pressure-induced changes in RBF and RVR at 0-5, 6-25 and 110-120 sec after step increase in MAP were used to assess the contribution of myogenic and TGF mechanisms and steady state autoregulation, respectively. The rate of the initial increase in RVR, attributed to the myogenic mechanism, was reduced by ~50% in m/m mice, indicating the speed of the myogenic response was inhibited. Steady state autoregulation was similar between ENaC +/+ and m/m mice. Although the rate of the secondary increase in RVR, attributed to TGF, was similar in ENaC +/+ and m/m mice, however, occurred over a longer period (+10 s), which may have allowed TGF to compensate for a loss in myogenic autoregulation. Our findings suggest ENaC is an important mediator of renal myogenic constriction mediated RBF autoregulation in-vivo.