Exercise training restores coronary arteriolar dilation to NOS activation distal to coronary artery occlusion: role of hydrogen peroxide.
OBJECTIVE
Exercise training has been shown to restore vasodilation to nitric oxide synthase (NOS) activation in arterioles distal to coronary artery occlusion. Because reactive oxygen species are generated during NOS uncoupling and the production of vasodilator H2O2 is increased during exercise in patients with coronary disease, we proposed that H2O2 may contribute to the restoration of vasodilation in porcine coronary occlusion model.


RESULTS
Left circumflex (LCX) coronary artery of miniature swine was progressively occluded for 8 weeks followed by exercise training (EX; 5 days/wk treadmill) or sedentary (SED) protocols for 12 weeks. Arterioles were isolated from distal LCX and nonoccluded left anterior descending (LAD) artery for in vitro study. Vasodilation to NOS activators adenosine and ionomycin was impaired in SED LCX, but not LAD, arterioles. This impairment was restored by L-arginine. NO production induced by adenosine was also reduced in SED LCX arterioles. EX had no effect on LAD arterioles but improved NO production and restored dilation of LCX arterioles. NOS blockade (L-NAME) inhibited vasodilation to NOS activators in LAD (SED & EX) arterioles but was ineffective in SED LCX arterioles. In EX LCX arterioles, vasodilation to NOS activators was slightly inhibited by L-NAME but abolished by catalase. H2O2 production was markedly increased by adenosine in EX LCX arterioles.


CONCLUSIONS
This study demonstrates that endothelium-dependent NO-mediated dilation is impaired in SED LCX arterioles and that EX training restores the impaired function. It appears that H2O2, in addition to NO, contributes significantly to EX-induced restoration of endothelium-dependent dilation of coronary arterioles distal to occlusion.
Thengchaisri
Naris
N
Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, College of Medicine, Texas A&M Health Science Center, 702 Southwest H.K. Dodgen Loop, Temple, TX 76504, USA.
Shipley
Robert
R
Ren
Yi
Y
Parker
Janet
J
Kuo
Lih
L
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles / Q000503:physiopathology*; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology*; D004789:Enzyme Activation; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D012146:Rest; D013552:Swine; D013556:Swine, Miniature; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000503:physiopathology
D016877:Oxidants; D009569:Nitric Oxide; D001120:Arginine; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase