Adaptations of the Endothelin System After Exercise Training in a Porcine Model of Ischemic Heart Disease

作者：Robles Juan Carlos; Heaps Cristine L^*

来源：Microcirculation, 2015, 22(1): 68-78.

DOI：10.1111/micc.12174

• coronary artery disease
• near-resistance arteries
• coronary artery occlusion
• stenosis

ObjectiveTo the test the hypothesis that exercise training would increase endothelin-mediated vasoconstriction in collateral-dependent arteries via enhanced contribution of ETA.
MethodsAn ameroid constrictor was surgically placed around the proximal LCX artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomized into sedentary or exercise-training (treadmill; 5days/week; 14weeks) groups. Subsequently, arteries (similar to 150m diameter) were isolated from collateral-dependent and nonoccluded myocardial regions and studied.
ResultsFollowing exercise training, ET-1-mediated contraction was significantly enhanced in collateral-dependent arteries. Exercise training induced a disproportionate increase in the ETA contribution to the ET-1 contractile response in collateral-dependent arteries, with negligible contributions by ETB. In collateral-dependent arteries of sedentary pigs, inhibition of ETA or ETB did not significantly alter ET-1 contractile responses in collateral-dependent arteries, suggesting compensation by the functionally active receptor. These adaptations occurred without significant changes in ETA, ETB, or ECE mRNA levels but with significant exercise-training-induced elevations in endothelin levels in both nonoccluded and collateral-dependent myocardial regions
ConclusionsTaken together, these data reveal differential adaptive responses in collateral-dependent arteries based upon physical activity level. ETA and ETB appear to compensate for one another to maintain contraction in sedentary pigs, whereas exercise-training favors enhanced contribution of ETA.

• 出版日期2015-1