TY - JOUR
T1 - Effect of exercise training on nitric oxide and superoxide/H 2O 2 signaling pathways in collateral-dependent porcine coronary arterioles
AU - Xie, Wei
AU - Parker, Janet L.
AU - Heaps, Cristine L.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - Endothelial nitric oxide (NO) synthase (NOS) has been shown to contribute to enhanced vascular function after exercise training. Recent studies have revealed that relatively low concentrations of reactive oxygen species can contribute to endothelium-dependent vasodilation under physiological conditions. We tested the hypothesis that exercise training enhances endothelial function via endotheliumderived vasodilators, NO and superoxide/H 2O 2, in the underlying setting of chronic coronary artery occlusion. An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary (penconfined) or exercise-training (treadmill-run: 5 days/wk for 14 wk) regimens. Exercise training significantly enhanced concentration-dependent, bradykinin-mediated dilation in cannulated collateral-dependent arterioles (∼130 μm diameter) compared with sedentary pigs. NOS inhibition reversed training-enhanced dilation at low bradykinin concentrations in collateral-dependent arterioles, although increased dilation persisted at higher bradykinin concentrations. Total and phosphorylated (Ser 1179) endothelial NOS protein levels were significantly increased in arterioles from collateral-dependent compared with the nonoccluded region, independent of exercise. The H 2O 2 scavenger polyethylene glycol-catalase abolished the trainingenhanced bradykinin-mediated dilation in collateral-dependent arterioles; similar results were observed with the SOD inhibitor diethyldithiocarbamate. Fluorescence measures of bradykinin-stimulated H 2O 2 levels were significantly increased by exercise training, independent of occlusion. The NADPH inhibitor apocynin significantly attenuated bradykinin-mediated dilation in arterioles of exercise-trained, but not sedentary, pigs and was associated with significantly increased protein levels of the NADPH subunit p67phox. These data provide evidence that, in addition to NO, the superoxide/H 2O 2 signaling pathway significantly contributes to exercise training-enhanced endothelium-mediated dilation in collateral-dependent coronary arterioles.
AB - Endothelial nitric oxide (NO) synthase (NOS) has been shown to contribute to enhanced vascular function after exercise training. Recent studies have revealed that relatively low concentrations of reactive oxygen species can contribute to endothelium-dependent vasodilation under physiological conditions. We tested the hypothesis that exercise training enhances endothelial function via endotheliumderived vasodilators, NO and superoxide/H 2O 2, in the underlying setting of chronic coronary artery occlusion. An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary (penconfined) or exercise-training (treadmill-run: 5 days/wk for 14 wk) regimens. Exercise training significantly enhanced concentration-dependent, bradykinin-mediated dilation in cannulated collateral-dependent arterioles (∼130 μm diameter) compared with sedentary pigs. NOS inhibition reversed training-enhanced dilation at low bradykinin concentrations in collateral-dependent arterioles, although increased dilation persisted at higher bradykinin concentrations. Total and phosphorylated (Ser 1179) endothelial NOS protein levels were significantly increased in arterioles from collateral-dependent compared with the nonoccluded region, independent of exercise. The H 2O 2 scavenger polyethylene glycol-catalase abolished the trainingenhanced bradykinin-mediated dilation in collateral-dependent arterioles; similar results were observed with the SOD inhibitor diethyldithiocarbamate. Fluorescence measures of bradykinin-stimulated H 2O 2 levels were significantly increased by exercise training, independent of occlusion. The NADPH inhibitor apocynin significantly attenuated bradykinin-mediated dilation in arterioles of exercise-trained, but not sedentary, pigs and was associated with significantly increased protein levels of the NADPH subunit p67phox. These data provide evidence that, in addition to NO, the superoxide/H 2O 2 signaling pathway significantly contributes to exercise training-enhanced endothelium-mediated dilation in collateral-dependent coronary arterioles.
KW - Chronic coronary occlusion
KW - Hydrogen peroxide
KW - Ischemic heart disease
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UR - http://www.scopus.com/inward/citedby.url?scp=84862101913&partnerID=8YFLogxK
U2 - 10.1152/japplphysiol.01248.2011
DO - 10.1152/japplphysiol.01248.2011
M3 - Article
C2 - 22323648
AN - SCOPUS:84862101913
SN - 8750-7587
VL - 112
SP - 1546
EP - 1555
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 9
ER -