Type 5 Adenylyl Cyclase Disruption Enhances Exercise Capacity Not Due To Improved Cardiac Output, But Rather To Resistance To Oxidative Stress In Skeletal Muscle

Improving exercise tolerance is one of major goals of physicians treating patients with cardiovascular disease. There are two broad mechanisms by which exercise performance can be enhanced: an increase in cardiac output (CO); alterations in energy metabolism in skeletal muscle. Less is known regarding specific molecular pathways that might be approached therapeutically to improve exercise tolerance. We examined exercise capacity in type 5 adenylyl cyclase knockout (AC5 KO) mice, which exhibit increased longevity and are protected against stress. The maximal distance run was significantly increased in AC5 KO compared to WT mice (n=13/group) (817±41m vs. 569±26m, p max ), an indicator of metabolic substrate utilization, was decreased in the AC5 KO group (0.92±0.02 vs 0.96±0.02; p