Role of DEG/ENaC in the renal myogenic response

DEG/ENaC 在肾生肌反应中的作用

• 批准号: 6995786
• 负责人: Nikki L Jernigan
• 金额: $ 3.71万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2006-05-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6995786
• 关键词: amiloride; cardiovascular pharmacology; confocal scanning microscopy; gene expression; genetically modified animals; kidney circulation; laboratory mouse; polymerase chain reaction; postdoctoral investigator; protein localization; protein structure function; renal artery; sodium channel; stretch reflex; vascular smooth muscle; vasoconstriction

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.

描述（由申请人提供）：肌源性反应是一种自动调节机制，有助于维持相对恒定的肾血流并保护肾脏免受与高血压相关的终末器官损伤。 肌源性反应是血管平滑肌（VSM）响应血管应变和与灌注压增加相关的血管壁机械拉伸而收缩的固有能力。 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，血管平滑肌去极化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。 尽管机械敏感离子通道被认为能够引发 VSM 拉伸诱导的去极化和收缩，但这些通道的分子特性尚不清楚。 最近的报告表明，感觉神经元的正常机械感觉需要退化蛋白/上皮 Na+ 通道 (DEG/ENaC)，然而，DEG/ENaC 蛋白在肌源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成分在调节 VSM 肌源性收缩和肾血流自动调节中的作用的重要新信息。