Abstract 13956: Physical Exercise Prior to Femoral Artery Ligation Stimulates Collateral Artery Growth in a Nitric Oxide-Dependent Manner
Background: Physical exercise is important in cardiovascular prevention and therapy. In arterial stenosis, exercise increases collateral flow by enhancing fluid shear stress. The effects of physical exercise prior to arterial occlusion are unknown.
Methods and Results: Mice were subjected to four weeks voluntary treadmill running before unilateral femoral artery ligation (FAL). Hindlimb perfusion was assessed using microspheres infusion under conditions of adenosine-induced maximal vasodilation, and expressed as percentages ligated/unligated hindlimb. Directly after FAL, perfusion fell to 3.5±0.7% in sedentary wildtype (C57/Bl6) mice. Exercise prior to FAL did not change perfusion acutely after ligation (4.0±0.8%). One week after FAL, perfusion was restored to 37.4±2.7% in the sedentary (“S”) group. Exercise until the final experiment (“run”, “R”) augmented perfusion restoration to 52.8±4.1% (p<0.005 compared to sedentary). When exercise was stopped at the time of FAL (“run and rest”, “RR”), perfusion recovery after one week was 50.3±4.7% (p<0.001 compared to S, p=ns compared to R). Similarly, number of collateral arterioles was increased in both R and RR. In collateral-containing hindlimbs, mRNA expression of inflammatory cytokines TNFalpha and MCP1 was reduced. mRNA-expression of inducible NO-synthase (iNOS) was increased to 179±40% (p<0.05) in R and to 172±34% (p<0.05) in RR mice. Endothelial NO-synthase activity (phospho-eNOS/total eNOS protein) was increased to 211±46 (p<0.05) in R and to 211±35% (p<0.05) in RR animals. eNOS-/- sedentary mice showed a strongly impaired perfusion restoration to 4.3±1.0% one week after FAL, which was stimulated by prior exercise (RR) to 8.2±0.8% (p<0.01 compared to S). iNOS-/- mice, while showing near to normal perfusion restoration at sedentary conditions (30.5±3.2%), failed to increase perfusion restoration by exercise.
Conclusion: Physical exercise before femoral artery occlusion reduces inflammatory cytokine expression and stimulates collateral artery growth in an NO-dependent manner. These data underline the vascular risk profile associated with a sedentary lifestyle and identify exercise as a prophylactic means to enhance vascular growth.
- © 2011 by American Heart Association, Inc.