Abstract
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.
Original language | English (US) |
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Pages (from-to) | 391-402 |
Number of pages | 12 |
Journal | Microcirculation |
Volume | 16 |
Issue number | 5 |
DOIs | |
State | Published - 2009 |
Externally published | Yes |
Keywords
- Blood flow
- Endothelium
- NO
- Oxidative stress
- Remodeling
- Resistance arteries
- Vasoconstriction
- Vasorelaxation
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)