Renal blood flow (RBF) autoregulation is mediated by two overlapping mechanisms, the fast acting myogenic response and the slower tubuloglomerular feedback (TGF). The fast acting myogenic response is thought to prevent transmission of systemic pressure to the renal microvasculature and prevent renal injury and related hypertension. Despite the physiological importance of the myogenic response, the molecular identity of the elements transducing vascular stretch into a cellular event remains unclear. Several candidates have been considered as transducers of vascular stretch into intracellular signaling. Our laboratory has focused on Epithelial Na+ Channel (ENaC) proteins because of their strong evolutionary link to mechanotransduction in the nematode, C. elegans. Previous studies from our lab suggest β protein (βENaC) plays an important role in myogenic constriction in certain arteries. Silencing of endogenous βENaC (siRNA, genetically modified mice) inhibits myogenic constriction. Mice with reduced levels of βENaC (βENaC m/m) have delayed whole kidney autoregulatory responses, even in the presence of active TGF, suggesting defective myogenic autoregulation. When TGF is suppressed following blood volume expansion, renal autoregulation is inhibited. In the absence of TGF, autoregulatory index at 2 min was significantly higher in the βENaC m/m mice (+0.45± 0.26 vs. -0.66 ± 0.32, p=0.0099). βENaC m/m mice have increased expression of inflammatory and remodeling markers, such as macrophage infiltration, IL1-β, IL6, TNFα collagen III and TGFβ. Furthermore, βENaC m/m mice increased mean arterial blood pressure (MAP, 120 ± 3 vs. 105 ± 2 mm Hg, p=0.016), as measured using radio telemetry. Our findings suggest βENaC is an important mediator of renal myogenic constriction mediated RBF autoregulation in-vivo and loss of the myogenic mechanism is associated with early signs of renal injury and increased MAP.