Objective—This study was to investigate the effects of chronic exercise on vasodilatation and endothelial intracellular calcium (EC [Ca²⁺]_i) signaling in atherosclerotic animals.

Methods and Results—For 8 weeks, male New Zealand White rabbits were fed rabbit chow with or without the addition of 2% cholesterol. They were further divided into control and exercise groups. Animals in the exercise groups ran on a leveled treadmill at 0.88 km/h for 10 to 60 minutes gradually for 5 days per week for a total of 8 weeks. At the end of experiments, femoral arteries were dissected, loaded with fura 2-AM, and mounted in a tissue flow chamber. PE-precontracted vessel specimens were exposed to acetylcholine (ACh). The EC [Ca²⁺]_i elevation and vasorelaxation were determined simultaneously under an epifluorescence microscope equipped with a ratio-imaging capability. Our results showed the following: (1) high cholesterol diet feeding caused lipid deposition on vascular surface, reduced the ACh-evoked EC [Ca²⁺]_i elevation, and impaired endothelium-dependent and endothelium-independent vascular responses, but chronic exercise had the opposite effects; (2) ACh-induced vasorelaxation was associated with EC [Ca²⁺]_i elevation in all groups; and (3) vasorelaxation at high levels of EC [Ca²⁺]_i elevation decreased in hypercholesterolemia.

Conclusions—Our data suggest that hypercholesterolemia induces vascular structural changes and impairs EC [Ca²⁺]_i signaling and vasodilatation, whereas chronic exercise partially reverses these adverse effects.