on September 20, 2004
Published online before print September 20, 2004, doi: 10.1161/01.HYP.0000144465.56360.ad
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Submitted on February 16, 2004
From the Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research (H.A.D.), University of Mississippi Medical Center, Jackson; and Department of Physiology and the Cardiovascular Research Center (D.G., D.R.H.), Medical College of Wisconsin, Milwaukee. * To whom correspondence should be addressed. E-mail: hdrummond{at}physiology.umsmed.edu.
Abstract--Mechanosensitive ion channels are thought to mediate stretch-induced contraction in vascular smooth muscle cells (VSMCs); however, the molecular identity of the mechanosensitive ion channel complex is unknown. Although recent reports suggest degenerin/epithelial Na+ channel (DEG/ENaC) proteins may be mechanosensors in sensory neurons, their role as mechanosensors in vascular tissue has not been examined. We first tested whether DEG/ENaC subunits are expressed in cerebral blood vessels and VSMCs and then examined their role as mechanosensors in mediating the myogenic response in intact blood vessels. Using RT-PCR, we found ENaC transcripts expressed in rat cerebral arteries and freshly dissociated rat cerebral VSMCs. We also detected ENaC expression in isolated blood vessels and VSMCs by immunoblotting and immunolocalization. Moreover, inhibition of ENaC with amiloride (1 µmol/L) and benzamil (30 nmol/L, 1 µmol), an amiloride analog, blocked myogenic constriction in isolated rat cerebral arteries. These data suggest that DEG/ENaC proteins are required for vessel responses to pressure and are consistent with the evolutionary conservation of mechanosensory function of DEG/ENaC proteins.
Revised on March 5, 2004
Degenerin/Epithelial Na+ Channel Proteins. Components of a Vascular Mechanosensor
Heather A. Drummond*;
Key words: autoregulation • muscle, smooth, vascular • mechanosensor • cerebral arteries
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