Impaired Coronary Endothelial Vasorelaxation in a Preclinical Model of Peripheral Arterial Insufficiency

The present study was designed to determine whether adult swine with peripheral artery insufficiency (PAI) would exhibit vascular dysfunction in vessels distinct from the affected distal limbs, the coronary conduit arteries. Moreover, we sought to evaluate the effect of exercise training on coronary vasomotor function in PAI. Eighteen female healthy young Yucatan miniature swine were randomly assigned to either occluded exercise trained (Occl-Ex, n = 7), or occluded-sedentary (Occl-Sed, n = 5), or non-occluded, non-exercised control (Non-Occl-Con, n=6) groups. Occl-Ex pigs were progressively trained by running on a treadmill (5 days/week, 12 weeks). The left descending artery (LAD) and left circumflex (LCX) coronary arteries were harvested. Vasorelaxation to adenosine diphosphate (ADP), bradykinin (BK), and sodium nitroprusside (SNP) were assessed in LAD’s; while constrictor responses to phenylephrine (PE), angiotensin II (Ang II), and endothelin-1 (ET-1) were assessed in LCX’s. Vasorelaxation to ADP was reduced in LADs from Occl-Sed and Occl-Ex pigs (P < 0.001) as compared to Non-Occl-Con pigs; however, Occl-Ex pigs exhibited partial recovery (P <0.001) intermediate to the other two groups. BK induced relaxation was reduced in LADs from Occl-Ex and Occl-Sed pigs (P < 0.001), compared to Non-Occl-Con, and exercise modestly increased responses to BK (P <0.05). In addition, SNP, PE, Ang II, and ET-1 responses were not significantly different among the groups. Our results indicate that ‘simple’ occlusion of the femoral arteries induces vascular dysfunction in conduit vessels distinct from the affected hindlimbs, as evident in blunted coronary vasorelaxation responses to ADP and BK. These findings imply that PAI, even in the absence of frank atherogenic vascular disease, contributes to vascular dysfunction in the coronary arteries that could exacerbate disease outcome in patients with peripheral artery disease. Further, regular daily physical activity partially recovered the deficit observed in the coronary arteries.