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Role of Mitochondrial Production of Reactive Oxygen Species on Angiotensin II Dependent Skeletal Muscle Angiogenesis.
Author(s) -
Stodola Timothy,
Joseph Joy,
Kalyanaraman Balaraman,
Greene Andrew
Publication year - 2009
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.23.1_supplement.625.8
Subject(s) - angiogenesis , reactive oxygen species , skeletal muscle , mitochondrion , chemistry , mitochondrial ros , endocrinology , medicine , scavenger , angiotensin ii , hindlimb , free radical scavenger , antioxidant , pharmacology , biology , biochemistry , receptor
Reactive oxygen species (ROS) play an essential role in physiological angiogenesis and are known to be produced in the mitochondria of working skeletal muscles. The goal of this study was to determine how dose‐dependent targeting of different sources of ROS could affect angiogenesis. To accomplish this we used TEMPOL, a general ROS scavenger, and Mito‐TEMPOL, a TEMPOL variant that has been demonstrated to accumulate in mitochondria. Seven week‐old Sprague‐Dawley rats were placed on 4% NaCl diet to suppress the Renin‐Angiotensin System. Electrical stimulators were implanted to intermittently stimulate the peroneal nerve in one hind leg, contracting the Tibialis Anterior (TA) and Extensor Digitorum Longus (EDL) muscles for 8 hours/day for 7 days while they were infused with ANGII at a subpressor dose. The rats were treated with TEMPOL (26.0 to 540.3 µmoles*kg −1 *day −1 ) or Mito‐TEMPOL (1.0 to 35.3 µmoles*kg −1 *day −1 ) in drinking water. Control rats had an 18.6% increase in microvessel density in the stimulated TA. Doses up to 118.9 of TEMPOL and 7.6 of Mito‐TEMPOL also had a significant increase in vessel density. Doses higher than 142.5 of TEMPOL and 11.6 of Mito‐TEMPOL suppressed the increase in vessel density. These data reinforce the importance of ROS in physiological angiogenesis and suggest that the source of ROS in ANGII and ES dependent angiogenesis is of mitochondrial origin. Supported by NIH HL 29587.