Chronic exercise reduces adhesion molecules/iNOS expression and partially reverses vascular responsiveness in hypercholesterolemic rabbit aortae

Abstract

To investigate exercise effects on the vascular function in hypercholesterolemia, male New Zealand White rabbits were divided into four groups; i.e. the normal diet control, the high cholesterol diet control, normal diet with exercise, and high cholesterol diet with exercise. High cholesterol diet groups were fed 2% cholesterol rabbit chow for 8 weeks. Animals of exercise groups ran on a treadmill at 0.88 km/h for 10–60 min/day, 5 day/week, and 8 weeks in total. Thoracic aortae were, then, isolated for functional and immunohistochemical analysis. We found that in rabbit aortae, (1) high cholesterol diet feeding caused lipid deposition and intimal thickening, induced expression of P-selectin, VCAM-1, MCP-1 and iNOS, and impaired acetylcholine (ACh)-evoked vasorelaxation; (2) exercise significantly reduced the protein expression of adhesion molecules/iNOS, and the intimal thickness in hypercholesterolemia; (3) chronic exercise enhanced ACh-evoked vasorelaxation in normal rabbits, but it only significantly improved vascular responses to the high dose (10 −6 M) of ACh in hypercholesterolemic rabbits; (4) both exercise and diet effects on vascular responses were mediated by altering the release of NO and endothelium-derived hyperpolarization factor. We conclude that exercise training decreases the expression of adhesion molecules and iNOS, and ameliorates the severe vascular dysfunction induced by high cholesterol feeding.