Continued divergence in V̇o_{2 max}of rats artificially selected for running endurance is mediated by greater convective blood O₂delivery

Abstract

We previously showed that after seven generations of artificial selection of rats for running capacity, maximal O2 uptake (VO2max) was 12% greater in high-capacity (HCR) than in low-capacity runners (LCR). This difference was due exclusively to a greater O2 uptake and utilization by skeletal muscle of HCR, without differences between lines in convective O2 delivery to muscle by the cardiopulmonary system (QO2max). The present study in generation 15 (G15) female rats tested the hypothesis that continuing improvement in skeletal muscle O2 transfer must be accompanied by augmentation in QO2max to support VO2max of HCR. Systemic O2 transport was studied during maximal normoxic and hypoxic exercise (inspired PO2 approximately 70 Torr). VO2max divergence between lines increased because of both improvement in HCR and deterioration in LCR: normoxic VO2max was 50% higher in HCR than LCR. The greater VO2max in HCR was accompanied by a 41% increase in QO2max: 96.1 +/- 4.0 in HCR vs. 68.1 +/- 2.5 ml stpd O2 x min(-1) x kg(-1) in LCR (P < 0.01) during normoxia. The greater G15 QO2max of HCR was due to a 48% greater stroke volume than LCR. Although tissue O2 diffusive conductance continued to increase in HCR, tissue O2 extraction was not significantly different from LCR at G15, because of the offsetting effect of greater HCR blood flow on tissue O2 extraction. These results indicate that continuing divergence in VO2max between lines occurs largely as a consequence of changes in the capacity to deliver O2 to the exercising muscle.

Fundamental questions about genes, inactivity, and chronic diseases

“…At the 15th generation, high-capacity runners that never exercise trained had 50, 41, and 48%, respectively, higher maximal aerobic capacity, maximal cardiac output, and maximal stoke volume than the untrained, low-capacity runners (43). Using the speculation that the higher aerobic capacity animals were more likely than the lower aerobic capacity to survive in an environment requiring exercise for survival to reproductive age, we speculate that natural selection could have chosen today's genotypes from those most physically fit to survive in the environment during the hundreds to thousands of years that humans have been on Earth.…”

Mechanisms underlying parallel reductions in aerobic capacity in non-migratory threespine stickleback (Gasterosteus aculeatus) populations

“…Garland, 1998;Hansen et al, 2006) and recent intraspecific empirical studies (e.g. Gonzalez et al, 2006;Chappell et al, 2007;Gębczynski and Konarzewski, 2011) argue that this is not the case. In particular, experimental evolution studies in rodents suggest that interspecific comparisons simply miss the step-wise evolution of aerobic capacity that can be observed at shorter time scales (e.g.…”

Effects of oxygen availability on maximum aerobic performance inMus musculusselected for basal metabolic rate or aerobic capacity

“…This points to step 4 (tissue capillary-to-cell diffusion) as limiting V O2,run in mice selected on V O2,swim and voluntary running (but not in mice selected on BMR, as their V O2,max elicited by exercise and thermogenesis did not differ). This view is further supported by results of studies on rats selected for divergent low-and high-endurance exercise capacity (Henderson et al, 2002;Howlet et al, 2003;Howlet et al, 2009;Gonzales et al, 2006). These studies demonstrated that the first structural and functional responses to selection enabling greater O 2 utilization in the high capacity runner line type were muscle adaptations that improved oxygen extraction, with little difference in O 2 delivery capacity at the level of heart and lungs (Henderson et al, 2002;Howlett et al, 2003).…”

“…However, further selection on low-and high-endurance exercise capacity resulted in substantial differences in pulmonary function (Kirkton et al, 2009) and cardiac output (Gonzales et al, 2006). Howlett et al therefore hypothesized that central factors (cardiovascular and/or pulmonary changes) could also become limiting during V O2,run ).…”

“…Several decades of studies on V O2,max have shown that the identification of limiting steps of O 2 delivery is not straightforward (Koteja, 1986;Henderson et al, 2002;Howlett et al, 2003;Seymour et al, 2004;Gonzales et al, 2006;Kirkton et al, 2009). A promising approach to identifying possible limits to V O2,max is offered by artificial selection experiments on metabolic rates (Swallow et al, 2009) (for reviews, see Garland and Rose, 2009;Garland et al, 2010).…”