Myogenic vasoconstriction in mouse renal interlobar arteries: role of endogenous beta and gammaENaC.
Mechanosensitive ion channels are thought to initiate pressure-induced vasoconstriction, however, the molecular identity of these channels is unknown. Recent work from our laboratory suggests that members of the Degenerin/Epithelial Na+ Channel (DEG/ENaC) family may be components of the mechanosensitive ion channel complex in vascular smooth muscle (VSM); however, the specific DEG/ENaC proteins mediating myogenic constriction are unknown. The goal of this study is to determine if specific knockdown of beta or gammaENaC, using dominant-negative (DN) or small-interference RNA (siRNA) molecules, inhibits pressure-induced vasoconstriction in mouse renal interlobar arteries. To address this goal, isolated arteries were transiently transfected with beta or gammaENaC DN-cDNA or siRNA molecules. After 24 h, vessels were either 1) cannulated and pressurized for pressure-diameter response curves or 2) dissociated and immunolabeled to determine VSM cell endogenous ENaC protein expression. We found that transfection of betaENaC DN-cDNA or siRNA suppresses beta-, but not gammaENaC protein expression. Similarly, gammaENaC DN-cDNA or siRNA suppresses gamma-, but not betaENaC protein expression. In addition, transfection of beta- or gammaENaC DN-cDNA or siRNA molecules inhibits pressure-induced vasoconstriction, but does not block agonist-induced vasoconstriction. Our results provide the first direct evidence that beta and gammaENaC proteins are essential in mediating myogenic vasoconstriction in mouse renal interlobar arteries.
Jernigan
Nikki L
NL
Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216, USA.
Drummond
Heather A
HA
D000818:Animals; D053503:Epithelial Sodium Channels / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D034741:RNA, Small Interfering; D012077:Renal Artery / Q000502:physiology*; D014162:Transfection; D014661:Vasoconstriction / Q000502:physiology*
D053503:Epithelial Sodium Channels; D034741:RNA, Small Interfering; C507049:Scnn1b protein, mouse; C507053:Scnn1g protein, mouse