Reactive Oxygen Species Are Necessary for High Flow (Shear Stress)‐induced Diameter Enlargement of Rat Resistance Arteries

Objectives: 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. Materials and 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 μm; 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.