Redox signaling of the arteriolar myogenic response.
Arteriolar vascular smooth muscle cells (VSMCs) are mechanosensitive, constricting to elevations in transmural pressure (P(TM)). The goal of the present study was to determine using mouse isolated tail arterioles and arteries whether oxidant signaling regulates this myogenic response. In response to P(TM) elevation, VSMCs of arterioles but not arteries generated constriction and increased reactive oxygen species (ROS) activity (using the H(2)O(2)-sensitive probe dichlorodihydrofluorescein). Arterioles had increased expression of NADPH oxidase components compared with arteries. Inhibition of NADPH oxidase, using mice with targeted impairment of enzyme components (p47(phox) or rac1) or diphenyleneiodonium, prevented the pressure-induced generation of ROS. When ROS activity was inhibited, either by inhibiting NADPH oxidase or with N-acetylcysteine, the myogenic constriction was abolished. The myogenic constriction was also inhibited by catalase, which inactivates H(2)O(2), but was unaffected by a cell-permeant mimic of superoxide dismutase (MnTMPyP). alpha(1)-Adrenergic constriction was not associated with altered ROS activity and was not affected by inhibition of NADPH oxidase or ROS. Exogenous H(2)O(2) constricted VSMCs of arterioles but not arteries. Thus, NADPH oxidase and ROS, in particular H(2)O(2), contribute to the myogenic response of arteriolar VSMCs.
Nowicki
P T
PT
Heart and Lung Research Institute, Ohio State University, Columbus, Ohio, USA.
Flavahan
S
S
Hassanain
H
H
Mitra
S
S
Holland
S
S
Goldschmidt-Clermont
P J
PJ
Flavahan
N A
NA
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction; D010208:Papaverine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009599:Nitroprusside; D006861:Hydrogen Peroxide; D010208:Papaverine; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine