Tempol, a superoxide dismutase mimetic, prevents cerebral vessel remodeling in hypertensive rats

Paulo Wagner Pires, Christian Deutsch, Jonathon Lee McClain, Curt Thomas Rogers, Anne Mc Laren Dorrance

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)445-452
Number of pages8
JournalMicrovascular Research
Volume80
Issue number3
DOIs
StatePublished - Dec 2010
Externally publishedYes

Keywords

  • Middle cerebral artery
  • SHRSP
  • Stroke
  • Tempol
  • Vascular remodeling

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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