Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries.
We tested two hypotheses, first that exercise training reverses age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries and second that this improved endothelium-dependent dilation is the result of increased nitric oxide (NO) bioavailability due to increased content and phosphorylation of endothelial NO synthase (eNOS) and/or increased antioxidant enzyme content. Young (2 mo) and old (22 mo) male Fischer 344 rats were exercise trained (Ex) or remained sedentary (Sed) for 10-12 wk, yielding four groups of rats: 1) young Sed (4-5 mo), 2) young Ex (4-5 mo), 3) old Sed (24-25 mo), and 4) old Ex (24-25 mo). Soleus muscle feed arteries (SFA) were isolated and cannulated with two glass micropipettes for examination of endothelium-dependent (ACh) and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. To determine the mechanism(s) by which exercise affected dilator responses, ACh-induced dilation was assessed in the presence of N(omega)-nitro-l-arginine (l-NNA; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), and l-NNA + Indo. Results indicated that ACh-induced dilation was blunted in old Sed SFA relative to young Sed SFA. Exercise training improved ACh-induced dilation in old SFA such that vasodilator responses in old Ex SFA were similar to young Sed and young Ex SFA. Addition of l-NNA, or l-NNA + Indo, abolished the exercise effect. Immunoblot analysis revealed that extracellular superoxide dismutase (SOD) protein content was increased by training in old SFA, whereas eNOS and SOD-1 protein content were not altered. Addition of exogenous SOD, or SOD + catalase, improved ACh-induced dilation in old Sed SFA such that vasodilator responses were similar to young Sed SFA. Addition of l-NNA abolished the effect of exogenous SOD in old Sed arteries. Collectively, these results indicate that exercise training reverses age-induced endothelial dysfunction in SFA by increasing NO bioavailability and that increases in vascular antioxidant capacity may play an integral role in the improvement in endothelial function.
Trott
Daniel W
DW
Department of Health and Kinesiology, Texas A&M University, College Station, TX 77843-4243, USA.
Gunduz
Filiz
F
Laughlin
M Harold
MH
Woodman
Christopher R
CR
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000109:Acetylcholine; D007213:Indomethacin