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1 Medicine, University of California, San Diego, La Jolla, California, United States
2 Biology, Union College, New York, New York, United States
3 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States
4 Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States
5 Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan, United States
6 La Jolla, California, United States; Medicine, University of California, San Diego, La Jolla, California, United States
* To whom correspondence should be addressed. E-mail: pdwagner{at}ucsd.edu.
Untrained rats selectively bred for either high (HCR) or low (LCR) treadmill running capacity previously demonstrated divergent physiological traits as early as the 7th generation (G7). We asked whether continued selective breeding to generation 15 (G15) would further increase the divergence in skeletal muscle capillarity, morphometry, and oxidative capacity seen previously at G7. At G15, mean body weight was significantly lower (p<0.001) in the HCR rats (n=11; 194+/-3g) than in LCR (n=12; 259+/-9g) while relative gastrocnemius muscle mass was not different (0.47+/-0.01 vs. 0.46+/-0.01% total body weight). Normoxic (FIO2=0.21) VO2max was 50% greater (p<0.001) in HCR despite the lower absolute muscle mass, and skeletal muscle O2 conductance (measured in hypoxia; FIO2=0.10) was 49% higher in HCR (p<0.001). Muscle oxidative enzyme activities were significantly higher in HCR (CS: 16.4+/-0.4 vs. 14.0+/-0.6;
-HAD: 5.2+/-0.2 vs. 4.2+/-0.2 mmol/kg/min). HCR rats had ~36% more total muscle fibers and also 36% more capillaries in the medial gastrocnemius. Because average muscle fiber area was 35% smaller, capillary density was 36% higher in HCR, but capillary/fiber ratio was the same. Compared to G7, G15 HCR animals showed 38% greater total fiber number with a further 25% decrease in mean fiber area. These data suggest that many of the skeletal muscle structural and functional adaptations enabling greater O2 utilization in HCR at G7 continue to progress following further selective breeding for endurance capacity. However, the largest changes at G15 relate to O2 delivery to skeletal muscle and not to the capacity of skeletal muscle to utilize O2 (6).
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