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

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 (1mM) for 6weeks. 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±1.25nM 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 80mmHg, tempol caused a dramatic increase in the MCA lumen diameter (246±5 vs. 207±3μm, p<0.001), outer diameter (281±5 vs. 241±3μm, 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.