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Exercise Training Rescues Impaired H 2 O 2 ‐Mediated Vasodilation in Collateral‐Dependent Coronary Arterioles Through Enhanced K + Channel Activation
Author(s) -
Johnson Kalen,
Bray Jeff,
Heaps Cristine
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02016
Subject(s) - vasodilation , medicine , cardiology , occlusion , circumflex , dilation (metric space) , artery , coronary artery disease , anatomy , geometry , mathematics
The objective of this study was to determine downstream cellular signaling pathways by which exercise training promotes H 2 O 2 ‐mediated dilation in arterioles distal to chronic coronary artery occlusion. We tested the hypothesis that exercise training would correct impaired H 2 O 2 ‐mediated dilation in collateral‐dependent arterioles through enhanced coupling of H 2 O 2 with voltage‐gated K + (Kv) and large‐conductance, calcium‐dependent K + (BKCa) channels. Yucatan miniature swine were surgically instrumented with an Ameroid constrictor around the proximal left circumflex coronary artery, which gradually induced occlusion and created a collateral‐dependent vascular bed. Arterioles from the left anterior descending artery region served as nonoccluded control vessels. Pigs were separated into two groups: one that underwent a progressive exercise training program (treadmill run; 5 days/week for 14 weeks) and another that remained sedentary and was limited to normal pen activity. Collateral‐dependent arterioles from sedentary pigs were significantly less sensitive to H 2 O 2 ‐induced dilation compared with nonoccluded arterioles (EC50: ‐4.55 ± 0.15 vs. ‐4.91 ± 0.15 log M, respectively; P<0.05), whereas this difference was eliminated after completion of the exercise training regimen when collateral‐dependent and nonoccluded arterioles responded similarly to H 2 O 2 (EC50: ‐4.86 ± 0.16 vs. ‐4.95 ± 0.18 log M, respectively). H 2 O 2 ‐mediated dilation in nonoccluded or collateral‐dependent arterioles from sedentary animals was not altered by inhibitors of Kv (4‐aminopyridine; 1 mM) or BKCa (iberiotoxin; 100 nM) channels. In contrast, after exercise training, Kv channels contributed significantly to dilation in nonoccluded arterioles and both Kv and BKCa channels played a significant role in dilation of collateral‐dependent arterioles. Interestingly, the contribution of Kv and BKCa channels to basal tone was not altered by occlusion or exercise training, suggesting similar availability of these channels in nonoccluded and collateral‐dependent arterioles of sedentary and exercise‐trained pigs. Immunoblot analysis was performed to assess levels of PKG dimerization, a potential mediator between H 2 O 2 and K + channels. These studies revealed that H 2 O 2 treatment significantly increased PKG dimerization in all artery treatment groups, and this effect was significantly greater in nonoccluded compared with collateral‐dependent arteries from sedentary pigs, but not different after exercise training. Taken together, our studies suggest that impaired H 2 O 2 ‐mediated vasodilation may be in part attributable to attenuated PKG dimerization in collateral‐dependent arterioles of sedentary pigs. However, while exercise training appeared to correct impaired H 2 O 2 ‐mediated dilation via enhanced coupling to K + channel activation, exercise‐induced changes in PKG dimerization did not appear to play a role.