Abstract 16977: Voluntary Exercise Prevents Cerebrovascular Dysfunction and the Changes in Compliance Associated with Severe Dyslipidemia in Mice
Many studies have associated the beneficial vascular effects of exercise in presence of cardiovascular risk factors with an up-regulation of the antioxidant defences, an increased NO bio-availability and a maintenance of the wall elasticity. Our knowledge of the underlying mechanisms for the benefits of exercise on the cerebral vasculature remains incomplete. We tested the hypothesis that voluntary exercise prevents cerebral endothelial dysfunction and the changes in cerebrovascular wall compliance associated with severe dyslipidemia in mice. Three-month old (m/o) severely dyslipidemic male mice spontaneously developing atherosclerosis (ATX, LDLR−/−, hApoB+/+ mice) and their wild type (WT) controls were exposed, or not, to 3 months of voluntary physical training (PT, approximately 6 km/day). Heart rate (HR) and blood pressure (BP) were recorded weekly in conscious animals by tail cuff. At 6-m/o, endothelium-dependent flow-mediated dilations (FMD) were assessed by measuring the diameter (D) variation of isolated pre-contracted pressurized cerebral arteries to flow (0–25 μl/min, approximately 0–20 dynes/cm2). Compliance was then measured in arteries bathed in a calcium-free physiological salt solution, by stepwise increases of the luminal pressure (P). Compliance is calculated as the strain [(D at Px)-(initial D)/(initial D)*100].
Results: are mean ± SEM of n=6 mice. At 6-m/o, PT tended to reduced HR (bpm) in WT and ATX mice (from 718±32 and 652±24, to 653±19 and 612±17, respectively, P=0.1) without reducing BP. Compared to WT, FMD was reduced in middle cerebral arteries isolated from ATX mice: for example, at 6.1±0.9 dynes/cm2, the dilation was reduced to 0.4±5.9% compared to 45±7% (P<0.05). PT, however, prevented this loss in FMD (27±7%, P<0.05). Cerebrovascular compliance was 34±1% greater at physiological pressures (40 to 120 mm Hg) in ATX compared to WT mice, a change which was normalized by PT (at 60 mm Hg; WT=52±5%, ATX=71±3% and ATX+PT =46±2%, P<0.05). These results demonstrate that voluntary exercise abrogated cerebral endothelial dysfunction and the changes in cerebrovascular compliance associated with severe dyslipidemia in mice. This is the first report of the normalization of the cerebrovascular compliance by exercise.
- © 2010 by American Heart Association, Inc.