Role of DEG/ENaC in the renal myogenic response

描述（由申请人提供）：肌原性反应是一种自我调节机制，有助于维持相对恒定的肾血流量，保护肾脏免受高血压相关的终末器官损伤。肌源性反应是血管平滑肌（VSM）固有的收缩能力，以响应与灌注压力增加相关的血管应变和血管壁的机械拉伸。先前的研究已经证实，肌源性血管收缩是由血管平滑肌（VSM）去极化引起的，它通过电压依赖性钙通道启动钙流入，从而激活平滑肌收缩装置。虽然机械敏感离子通道被认为启动VSM拉伸诱导的去极化和收缩，但这些通道的分子身份尚不清楚。最近的报道表明，Degenerin/上皮Na+通道（DEG/ENaC）是感觉神经元正常机械感觉所必需的，然而，DEG/ENaC蛋白在肌原性收缩中的作用尚未确定。我们假设DEG/ENaC蛋白是VSM中的机械传感器，是肾肌源性血管收缩所必需的。预计这些研究将产生关于DEG/ENaC蛋白作为机械敏感离子通道组分在调节VSM肌原性收缩和肾血流自动调节中的作用的重要新信息。

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.