Role of DEG/ENaC in the renal myogenic response

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DESCRIPTION (provided by applicant): The myogenic response is an autoregulatory mechanism that contributes to the maintenance of relatively constant renal blood flow and protects the kidney from end-organ damage associated with hypertension. The myogenic response is the inherent ability of vascular smooth muscle (VSM) to contract in response to vascular strain and mechanical stretch of the vessel wall associated with increased perfusion pressure. Previous studies have established that myogenic vasoconstriction results from depolarization of vascular smooth muscle (VSM) which initiates calcium influx via voltage-dependent calcium channels, thereby activating the smooth muscle contractile apparatus. Although mechanosensitive ion channels are thought to initiate VSM stretch-induced depolarization and contraction, the molecular identity of these channels is unknown. Recent reports suggest Degenerin/Epithelial Na+ Channels (DEG/ENaC) are required for normal mechanosensation in sensory neurons, however, the role of DEG/ENaC proteins in myogenic constriction has not been established. We hypothesized that DEG/ENaC proteins are mechanosensors in VSM and required for renal myogenic vasoconstriction. It is expected these studies will generate significant new information regarding the role of DEG/ENaC protein as components of mechanosensitive ion channels in the regulation of VSM myogenic constriction and the autoregulation of renal blood flow.