期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 289, 期 4, 页码 F891-F901出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00019.2005
关键词
mechanotransduction; renal blood flow autoregulation; amiloride; benzamil; isolated renal vessel; stretch-activated cation channel; calcium; sodium
资金
- NHLBI NIH HHS [HL-51971, HL-071603] Funding Source: Medline
The myogenic response is an essential component of renal blood flow autoregulation and is the inherent ability of vascular smooth muscle cells (VSMCs) to contract in response to increases in intraluminal pressure. Although mechanosensitive ion channels are thought to initiate VSMC stretch-induced contraction, their molecular identity is unknown. Recent reports suggest degenerin/epithelial Na+ channels (DEG/ENaC) may form mechanotransducers in sensory neurons and VSMCs; however, the role of DEG/ENaC proteins in myogenic constriction of mouse renal arteries has not been established. To test the hypothesis that DEG/ENaC proteins are required for myogenic constriction in renal vessels, we first determined expression of ENaC transcripts and proteins in mouse renal VSMCs. Then, we determined pressure- and agonist-induced constriction and changes in vascular smooth muscle cytosolic Ca2+ and Na+ in isolated mouse renal interlobar arteries following DEG/ENaC inhibition with amiloride and benzamil. We detect alpha-, beta-, and gamma ENaC transcript and protein expression in cultured mouse renal VSMC. In contrast, we detect only beta- and gamma- but not alpha ENaC protein in freshly dispersed mrVMSC. Selective DEG/ ENaC inhibition, with low doses of amiloride and benzamil, abolishes pressure- induced constriction and increases in cytosolic Ca2+ and Na+ without diminishing agonist-induced responses in isolated mouse interlobar arteries. Our findings indicate that DEG/ ENaC proteins are required for myogenic constriction in mouse interlobar arteries and are consistent with our hypothesis that DEG/ ENaC proteins may be components of mechanosensitive ion channel complexes required for myogenic vasoconstriction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据