TY - JOUR
T1 - Tempol, a superoxide dismutase mimetic, prevents cerebral vessel remodeling in hypertensive rats
AU - Pires, Paulo Wagner
AU - Deutsch, Christian
AU - McClain, Jonathon Lee
AU - Rogers, Curt Thomas
AU - Dorrance, Anne Mc Laren
N1 - Funding Information:
The present study was supported by grants from the National Institutes of Health ( HL077385 , to AMD) and the American Heart Association ( 0840122N , to AMD).
PY - 2010/12
Y1 - 2010/12
N2 - Increased reactive oxygen species (ROS) production is involved in the pathogenesis of hypertension and stroke. The effects of ROS on cerebral vessels from hypertensive rats have not been studied. We hypothesized that tempol, a superoxide dismutase mimetic, would prevent middle cerebral artery (MCA) remodeling in stroke-prone spontaneously hypertensive rats (SHRSP). Six-week-old male SHRSP were treated with tempol (1. mM) for 6. weeks. The MCA was then removed and mounted in a pressure myograph to study tone generation, vessel reactivity, and passive vessel structure. Data are shown as mean ± SEM, tempol vs. control. Plasma thiobarbituric acid reactive substances (TBARS) were decreased by tempol treatment (14.15 ± 1.46 vs. 20.55 ± 1.25. nM of malondialdehyde [MDA]/ml, p= 0.008). Maximum serotonin-induced constriction was increased by tempol treatment, without changes in dilation to adenosine diphosphate or tone generation. At an intralumenal pressure of 80. mm. Hg, tempol caused a dramatic increase in the MCA lumen diameter (246 ± 5 vs. 207 ± 3 μm, p< 0.001), outer diameter (281 ± 5 vs. 241 ± 3 μm, p< 0.001), lumen cross-sectional area, and vessel cross-sectional area. Collagen IV mRNA expressions were increased by 2.4-fold after tempol treatment. These results suggest that ROS are involved in the remodeling of the cerebral vasculature of SHRSP and that ROS scavenging can attenuate this process.
AB - Increased reactive oxygen species (ROS) production is involved in the pathogenesis of hypertension and stroke. The effects of ROS on cerebral vessels from hypertensive rats have not been studied. We hypothesized that tempol, a superoxide dismutase mimetic, would prevent middle cerebral artery (MCA) remodeling in stroke-prone spontaneously hypertensive rats (SHRSP). Six-week-old male SHRSP were treated with tempol (1. mM) for 6. weeks. The MCA was then removed and mounted in a pressure myograph to study tone generation, vessel reactivity, and passive vessel structure. Data are shown as mean ± SEM, tempol vs. control. Plasma thiobarbituric acid reactive substances (TBARS) were decreased by tempol treatment (14.15 ± 1.46 vs. 20.55 ± 1.25. nM of malondialdehyde [MDA]/ml, p= 0.008). Maximum serotonin-induced constriction was increased by tempol treatment, without changes in dilation to adenosine diphosphate or tone generation. At an intralumenal pressure of 80. mm. Hg, tempol caused a dramatic increase in the MCA lumen diameter (246 ± 5 vs. 207 ± 3 μm, p< 0.001), outer diameter (281 ± 5 vs. 241 ± 3 μm, p< 0.001), lumen cross-sectional area, and vessel cross-sectional area. Collagen IV mRNA expressions were increased by 2.4-fold after tempol treatment. These results suggest that ROS are involved in the remodeling of the cerebral vasculature of SHRSP and that ROS scavenging can attenuate this process.
KW - Middle cerebral artery
KW - SHRSP
KW - Stroke
KW - Tempol
KW - Vascular remodeling
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U2 - 10.1016/j.mvr.2010.06.004
DO - 10.1016/j.mvr.2010.06.004
M3 - Article
C2 - 20600163
AN - SCOPUS:78249260878
SN - 0026-2862
VL - 80
SP - 445
EP - 452
JO - Microvascular Research
JF - Microvascular Research
IS - 3
ER -