Limited Exercise Capacity in Heterozygous Manganese Superoxide Dismutase Gene–Knockout Mice

Publisher Website
Google Scholar
Abstract
Background— We have reported that there is a limitation of exercise capacity in mice with defects in the expression of endothelial nitric oxide (NO) synthase, which is associated with a greater increase in whole-body oxygen consumption (V̇o2). We hypothesized that in states in which superoxide anion (O2−) is increased, especially in the mitochondria, whole-body V̇o2 will be increased because of the inactivation of NO, and consequently, exercise capacity will be reduced. Methods and Results— Heterozygous manganese superoxide anion dismutase (SOD2) gene–knockout mice (SOD2+/−), in which SOD2 activity is reduced by 30% to 80%, and wild-type control mice (SOD2+/+) were treadmill-tested to measure indices defining exercise capacity. Tempol was given to each mouse for 7 days by an intraperitoneal injection to scavenge O2− before a second treadmill testing. V̇o2 and carbon dioxide production (V̇co2) at rest were increased in SOD2+/−. The work (vertical distance run × body weight) to exhaustion was decreased in S...