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Potential role of mitochondria in myogenic response of rat middle cerebral arteries
Author(s) -
Pratt Phillip F,
Chang Jeff K,
Narayanan Jayashree,
Clark Peter,
Gebremedhin Debebe,
Harder David R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a296
Subject(s) - cerebral arteries , myogenic contraction , anatomy , chemistry , neuroscience , cardiology , medicine , biology , smooth muscle
Many organs like the brain and kidney rely upon intrinsic mechanisms to regulate blood flow over a broad blood pressure range. This autoregulation of blood flow, or myogenic response, is important in protection of the organ from barotrauma as well as providing optimal delivery of nutrients and removal of waste products. The aim of this study was to test the hypothesis that reactive oxygen species are involved in the myogenic response. Pressurized, cannulated rat middle cerebral arteries (MCAs) were used to measure changes in vessel diameter in response to increases in intraluminal pressure. Vessels were treated with the free radical scavenger 4, hydroxyl‐2,2,6,6‐tetramethylpiperidine 1‐oxyl (tempol) to assess the role of superoxide anion in the autoregulatory response of rat MCAs. In the presence of 100 μM tempol, pressure‐induced vasoconstriction was significantly impaired as compared to MCAs not treated with tempol. This effect of tempol was reversible as determined by washout experiments. We also investigated the hypothesis that the mitochondria are a source of superoxide anion by using a novel mitochondrial targeted form of tempol (Mito‐tempol). We found a concentration‐related effect of Mito‐tempol to significantly impair the autoregulatory response of MCAs. These results suggest that superoxide anion plays an important role in the myogenic response of MCAs and that the mitochondria are a likely source of this free radical. These studies were made possible due to funding provided by NHLBI Grants HL33833‐17, HL59996‐05, HL68769‐02 and VA Merit Review Grants 3440‐02P and the MCW Medical Student Summer Research Program (MSSRP).