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.

说明(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脏血流，并保护肾脏免受与高血压相关的终末器官损害。肌源性反应是血管平滑肌(VSM)固有的收缩能力，以应对血管应变和与灌流压力增加相关的血管壁机械拉伸。以往的研究已经证实，肌源性血管收缩是血管平滑肌去极化的结果，它通过电压依赖性钙通道启动钙内流，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了VSM拉伸引起的去极化和收缩，但这些通道的分子同一性尚不清楚。最近的报道表明，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中的机械感受器，是肾脏肌源性血管收缩所必需的。这些研究有望为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提供重要的新信息。