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Am J Physiol Heart Circ Physiol 276: H1346-H1354, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 4, H1346-H1354, April 1999

Impaired aerobic capacity in hypercholesterolemic mice: partial reversal by exercise training

Josef Niebauer1,2, Andrew J. Maxwell1,3, Patrick S. Lin1, Philip S. Tsao1, Jon Kosek4, Daniel Bernstein3, and John P. Cooke1

1 Section of Vascular Medicine, Division of Cardiovascular Medicine and 3 Division of Pediatric Cardiology, Stanford University, and 4 Department of Pathology, Veterans Administration Hospital, Stanford University, Stanford, California 94305; and 2 Department of Cardiology, Heart Center, University of Leipzig, 04289 Leipzig, Germany

The present study assessed whether impaired aerobic capacity previously observed in hypercholesterolemic mice is reversible by exercise training. Seventy-two 8-wk-old female C57BL/6J wild-type (+, n = 42) and apolipoprotein E-deficient (-, n = 30) mice were assigned to the following eight interventions: normal chow, sedentary (E+, n = 17; E-, n = 8) or exercised (E+ex, n = 13; E-ex, n = 7) and high-fat chow, sedentary (E+chol, n = 6; E-chol, n = 8) or exercised (E+chol-ex, n = 6; E-chol-ex, n = 7). Mice were trained on a treadmill 2 × 1 h/day, 6 days/wk, for 4 wk. Cholesterol levels correlated inversely with maximum oxygen uptake (r = -0.35; P < 0.02), which was blunted in all hypercholesterolemic sedentary groups (all P < 0.05). Maximum oxygen uptake improved in all training groups but failed to match E+ex (all P < 0.05). Vascular reactivity and nitric oxide (NO) synthesis correlated with anaerobic threshold (r = 0.36; P < 0.025) and maximal distance run (r = 0.59; P < 0.007). We conclude that genetically induced hypercholesterolemia impairs aerobic capacity. This adverse impact of hypercholesterolemia on aerobic capacity may be related to its impairment of vascular NO synthesis and/or vascular smooth muscle sensitivity to nitrovasodilators. Aerobic capacity is improved to the same degree by exercise training in normal and genetically hypercholesterolemic mice, although there remains a persistent difference between these groups after training.

apolipoprotein E-deficient mice; atherosclerosis; nitric oxide; oxygen uptake; vascular reactivity


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