Reactive oxygen species are necessary for high flow (shear stress)-induced diameter enlargement of rat resistance arteries.
OBJECTIVE
Chronic increases in blood flow induce remodeling associated with increases in diameter and endothelium-mediated dilation. Remodeling requires cell growth and migration, which may involve reactive oxygen species (ROS). Nevertheless, the role of ROS in flow-mediated remodeling in resistance arteries is not known.


METHODS
Rat mesenteric resistance arteries (MRAs) were exposed to high flow (HF) by sequentially ligating second-order MRAs in vivo. After three weeks, arteries were collected for structural, pharmacological, and biochemical analysis.


RESULTS
In HF arteries, luminal diameter (431+/-12 to 553+/-14 microm; n=10), endothelium (acetylcholine)-mediated vasodilatation (61+/-6 to 77+/-6% relaxation) and NAD(P)H subunit (gp91phox and p67phox) expression levels, and ROS (dihydroethydine microphotography) and peroxynitrite (3-nitro-tyrosine) production were higher than in normal flow arteries. Acute ROS scavenging with tempol improved acetylcholine-dependent relaxation (92+/-4% relaxation), confirming that ROS are produced in HF arteries. Chronic treatment with tempol prevented the increase in diameter, reduced ROS and peroxynitrite production, and improved endothelium-mediated relaxation in HF arteries. Thus, ROS and NO were involved in HF-induced diameter enlargement, possibly through the formation of peroxynitrite, while ROS reduced the increase in endothelium-dependent relaxation.


CONCLUSIONS
ROS production is necessary for flow-mediated diameter enlargement of resistance arteries. However, ROS counteract, in part, the associated improvement in endothelium-mediated relaxation.
INSERM, Angers, France.
Eric J
EJ
Belin de Chantemèle
Emilie
E
Vessières
Odile
O
Dumont
Anne-Laure
AL
Guihot
Bertrand
B
Toutain
Laurent
L
Loufrani
Daniel
D
Henrion
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008638:Mesenteric Arteries / Q000502:physiology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D033081:Shear Strength / Q000187:drug effects / Q000502:physiology; D013113:Spin Labels; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D013113:Spin Labels; D014665:Vasodilator Agents; C079789:neutrophil cytosol factor 67K; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000109:Acetylcholine; C001803:tempol