Effects of ischemic heart disease and exercise training on mechanisms of nitric oxide production

Abstract

Control and collateral‐dependent coronary arteries of exercise trained swine display enhanced nitric oxide‐dependent bradykinin‐mediated relaxation. For this study, we hypothesized that exercise training elicits cellular adaptations to enhance nitric oxide production in coronary arteries of ischemic hearts. Ameroid constrictors were placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniswine. Collateral‐dependent (LCX) and control (nonoccluded left anterior descending) arteries (∼1–2 mm diam) were isolated from sedentary and exercise trained (treadmill; 14 wks) pigs. Endothelial cells were dissociated and intracellular Ca2+ (fura‐2) responses to bradykinin were studied. Caveolin‐1 and eNOS protein levels were evaluated by immunoblot. Exercise training significantly enhanced bradykinin‐stimulated Ca2+ levels in cells of both control and collateral‐dependent arteries. Caveolin‐1 protein was significantly elevated in collateral‐dependent arteries of sedentary pigs; an increase that was reversed with exercise training. eNOS protein was not altered by occlusion or exercise training. Our studies suggest that increased bradykinin‐stimulated endothelial Ca2+ levels and reduced caveolin‐1 protein contribute to improved bradykinin‐mediated relaxation in both control and collateral‐dependent arteries of exercise trained swine. NIH HL64931