Exercise Training-Enhanced, Endothelium-Dependent Dilation Mediated by Altered Regulation of BK_Ca Channels in Collateral-Dependent Porcine Coronary Arterioles

Objective: Test the hypothesis that exercise training increases the contribution of BK_Ca channels to endothelium-mediated dilation in coronary arterioles from collateral-dependent myocardial regions of chronically occluded pig hearts and may function downstream of H₂O₂. Methods: An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary or exercise training (treadmill; 14 week) regimens. Results: Exercise training significantly enhanced bradykinin-mediated dilation in collateral-dependent arterioles (~125 μm diameter) compared with sedentary pigs. The BK_Ca-channel blocker, iberiotoxin alone or in combination with the H₂O₂ scavenger, polyethylene glycol catalase, reversed exercise training-enhanced dilation in collateral-dependent arterioles. Iberiotoxin-sensitive whole-cell K⁺ currents (i.e., BK_Ca-channel currents) were not different between smooth muscle cells of nonoccluded and collateral-dependent arterioles of sedentary and exercise trained groups. Conclusions: These data provide evidence that BK_Ca-channel activity contributes to exercise training-enhanced endothelium-dependent dilation in collateral-dependent coronary arterioles despite no change in smooth muscle BK_Ca-channel current. Taken together, our findings suggest that a component of the bradykinin signaling pathway, which stimulates BK_Ca channels, is enhanced by exercise training in collateral-dependent arterioles and suggest a potential role for H₂O₂ as the mediator.