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Articles in PresS, published online ahead of print December 13, 2002
J Appl Physiol, 10.1152/jap.00556.2002
Submitted on June 25, 2002
Accepted on December 7, 2002
1 Department of Medicine, University of California-San Diego, La Jolla, CA, USA
2 Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA
3 Physiology and Molecular Medicine, Medical College of Ohio, Toledo, OH, USA
* To whom correspondence should be addressed. E-mail: rhowlett{at}ucsd.edu.
To attempt to explain the difference in intrinsic (untrained) endurance running capacity in rats selectively bred over 7 generations for either low (LCR) or high (HCR) running capacity, the relationship between skeletal muscle capillarity, fiber composition, enzyme activity, and oxygen transport was studied. Ten females from each group (body wt: 228 g (HCR), 247 g (LCR); p=0.03) were studied at 25 weeks of age. Peak normoxic VO2 max and muscle O2 conductance were previously reported to be 12% and 33% higher, respectively, in HCR, despite similar ventilation, arterial O2 saturation, and a cardiac output that was only 10% greater in HCR compared to LCR. Total capillary and fiber number in the medial gastrocnemius were similar in HCR and LCR, but because fiber area was 37% lower in HCR, the number of capillaries per unit area (or mass) of muscle was higher in HCR by 32% (p<0.001). A positive correlation (r = 0.92) was seen between capillary density and muscle oxygen conductance. Skeletal muscle enzymes citrate synthase (CS) and 
-hydroxyacyl-CoA dehydrogenase (-HAD) were both about 40% higher (p<0.001) in HCR (CS: 12.4 ± 0.7 vs. 8.7 ± 0.4; -HAD: 3.4 ± 0.2 vs. 2.4 ± 0.2 mmol/kg/min,) while phosphofructokinase (PFK) was significantly (p = 0.02) lower in HCR (27.8 ± 1.2 vs. 35.2 ± 2.5 mmol/kg/min) and hexokinase (HK) was the same (0.65 ± 0.04 vs. 0.65 ± 0.03 mmol/kg/min). Resting muscle ATP, phosphocreatine (PCr), and glycogen contents were not different between groups. Taken together, these data suggest that in rats selectively bred for high endurance exercise capacity, most of the enabling adaptations occur peripherally in the skeletal muscles, matching structure to function, and not in differences at the level of he heart or lung.
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