New insights into the vascular mechanisms underlying the beneficial effect of swimming training on the endothelial vasodilator function in apolipoprotein E-deficient mice.
The antiatherogenic role of exercise is poorly understood. We examined the swimming exercise-induced vascular mechanisms which enhance the endothelial vasodilator function in apoE(-/-) mice. Male apoE(-/-) mice treated for 9 weeks with a lipid-rich diet were divided into two groups: the exercise group (apoE(-/-) X), which underwent a 9-week swimming protocol (50 min/day; 5days/week) and the sedentary group (apoE(-/-) S). C57BL/6 mice were used as the control group. Atherosclerotic lesions in the aortic roots were significantly reduced in apoE(-/-) X compared to apoE(-/-) S. Relaxation to acetylcholine was improved in apoE(-/-) X as compared to apoE(-/-) S and control mice with E(max) and pD(2) values significantly higher. pD(2) values in response to papaverine were higher in apoE(-/-) X than in the other groups. Relaxation in response to A23187 and DEA-NONOate were similar. These findings suggest that swimming training may increase the sensitivity of relaxation to acetylcholine, which in turn activates acetylcholine-mediated signaling pathways leading to increased NO bioactivity. Swimming may also prolong the signaling actions of NO by stimulating the sensitivity of vascular smooth muscle cells to cyclic nucleotides. These appear to be the key mechanisms underlying the improvement of the NO-cGMP pathway in exercised apoE(-/-) mice.
Pellegrin
Maxime
M
EA 3921 Optimisation Métabolique et Cellulaire, Université de Franche-Comté, UFR Médecine-Pharmacie/STAPS, place Saint Jacques, 25030 Besançon, France. maxime.pellegrin@univ-fcomte.fr
Berthelot
Alain
A
Houdayer
Christophe
C
Gaume
Vincent
V
Deckert
Valérie
V
Laurant
Pascal
P
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000502:physiology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010805:Physical Conditioning, Animal / Q000379:methods*; D013550:Swimming; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001057:Apolipoproteins E; D006834:Hydrazines; D020030:Nitric Oxide Donors; D014280:Triglycerides; D014665:Vasodilator Agents; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D006152:Cyclic GMP; D000109:Acetylcholine