Continued divergence in V̇O 2 max of rats artificially selected for running endurance is mediated by greater convective blood O 2 delivery

Gonzalez, Norberto C., Scott D. Kirkton, Richard A. Howlett, Steven L. Britton, Lauren G. Koch, Harrieth E. Wagner, and Peter D. Wagner. Continued divergence in V̇O2 max of rats artificially selected for running endurance is mediated by greater convective blood O2 delivery. J Appl Physiol 101: 1288–1296, 2006. First published June 15, 2006; doi:10.1152/japplphysiol.01527.2005.—We previously showed that after seven generations of artificial selection of rats for running capacity, maximal O2 uptake (V̇O2 max) 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 (Q̇O2 max). 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 Q̇O2 max to support V̇O2 max of HCR. Systemic O2 transport was studied during maximal normoxic and hypoxic exercise (inspired PO2 70 Torr). V̇O2 max divergence between lines increased because of both improvement in HCR and deterioration in LCR: normoxic V̇O2 max was 50% higher in HCR than LCR. The greater V̇O2 max in HCR was accompanied by a 41% increase in Q̇O2 max: 96.1 4.0 in HCR vs. 68.1 2.5 ml STPD O2 min 1 kg 1 in LCR (P 0.01) during normoxia. The greater G15 Q̇O2 max 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 V̇O2 max between lines occurs largely as a consequence of changes in the capacity to deliver O2 to the exercising muscle.

[1]  L. Koch,et al.  Animal models of complex diseases: An initial strategy , 2005, IUBMB life.

[2]  Ø. Ellingsen,et al.  Cardiovascular Risk Factors Emerge After Artificial Selection for Low Aerobic Capacity , 2005, Science.

[3]  V. Froelicher,et al.  Fitness versus physical activity patterns in predicting mortality in men. , 2004, The American journal of medicine.

[4]  K. Georgieva,et al.  Effects of nandrolone decanoate on VO2max, running economy, and endurance in rats. , 2004, Medicine and science in sports and exercise.

[5]  Ø. Ellingsen,et al.  Aerobic Fitness Is Associated With Cardiomyocyte Contractile Capacity and Endothelial Function in Exercise Training and Detraining , 2004, Circulation.

[6]  J. Richalet,et al.  Effects of exercise training on acclimatization to hypoxia: systemic O2 transport during maximal exercise. , 2003, Journal of applied physiology.

[7]  P. Lloyd,et al.  Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. , 2003, American journal of physiology. Heart and circulatory physiology.

[8]  R. A. Howlett,et al.  Selected contribution: skeletal muscle capillarity and enzyme activity in rats selectively bred for running endurance. , 2003, Journal of applied physiology.

[9]  T. Garland,et al.  Artificial selection for high activity favors mighty mini-muscles in house mice. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[10]  L. Koch,et al.  Determinants of maximal O(2) uptake in rats selectively bred for endurance running capacity. , 2002, Journal of applied physiology.

[11]  Jason G. Belter,et al.  EVOLUTION OF A SMALL‐MUSCLE POLYMORPHISM IN LINES OF HOUSE MICE SELECTED FOR HIGH ACTIVITY LEVELS , 2002, Evolution; international journal of organic evolution.

[12]  Victor F. Froelicher,et al.  Exercise capacity and mortality among men referred for exercise testing. , 2002, The New England journal of medicine.

[13]  L. Koch,et al.  Cardiac function in rats selectively bred for low- and high-capacity running. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[14]  L. Koch,et al.  Artificial selection for intrinsic aerobic endurance running capacity in rats. , 2001, Physiological genomics.

[15]  L. Koch,et al.  Animal Genetic Models for Complex Traits of Physical Capacity , 2001, Exercise and sport sciences reviews.

[16]  A. Biewener,et al.  Physiology: Exercise and reduced muscle mass in starlings , 2000, Nature.

[17]  N. Gonzalez,et al.  Acute vs. chronic effects of elevated hemoglobin O(2) affinity on O(2) transport in maximal exercise. , 2000, Journal of applied physiology.

[18]  P. Wagner,et al.  Structural basis of muscle O(2) diffusing capacity: evidence from muscle function in situ. , 2000, Journal of applied physiology.

[19]  C. Bouchard,et al.  Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study. , 2000, Journal of applied physiology.

[20]  J A Dempsey,et al.  Exercise-induced arterial hypoxemia. , 1999, Journal of applied physiology.

[21]  C. Bouchard,et al.  Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. , 1999, Journal of applied physiology.

[22]  N. Gonzalez,et al.  Effect of chronic sodium cyanate administration on O2 transport and uptake in hypoxic and normoxic exercise. , 1999, Journal of applied physiology.

[23]  B. Saltin,et al.  Left ventricular function in endurance runners during exercise. , 1998, Acta physiologica Scandinavica.

[24]  P. Wagner,et al.  A theoretical analysis of factors determining VO2 MAX at sea level and altitude. , 1996, Respiration physiology.

[25]  M. Laughlin,et al.  Regional changes in capillary supply in skeletal muscle of high-intensity endurance-trained rats. , 1996, Journal of applied physiology.

[26]  J. Leigh,et al.  Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport. , 1995, The Journal of clinical investigation.

[27]  P. Wagner,et al.  Effect of hematocrit on systemic O2 transport in hypoxic and normoxic exercise in rats. , 1994, Journal of applied physiology.

[28]  J. Piiper,et al.  Pulmonary gas exchange during hypoxic exercise in the rat. , 1994, Respiration physiology.

[29]  P. Wagner Algebraic analysis of the determinants of VO2,max. , 1993, Respiration physiology.

[30]  Anthony James Woakes,et al.  Respiratory and cardiovascular adjustments during exercise of increasing intensity and during recovery in thoroughbred racehorses. , 1993, The Journal of experimental biology.

[31]  P W Hochachka,et al.  Capillary-to-fiber geometry and mitochondrial density in hummingbird flight muscle. , 1992, Respiration physiology.

[32]  J. Roca,et al.  Evidence for tissue diffusion limitation of VO2max in normal humans. , 1989, Journal of applied physiology.

[33]  C. Honig,et al.  Minimum intracellular PO2 for maximum cytochrome turnover in red muscle in situ. , 1987, The American journal of physiology.

[34]  C. Bouchard,et al.  Aerobic performance in brothers, dizygotic and monozygotic twins. , 1986, Medicine and science in sports and exercise.

[35]  C. Hansen,et al.  Development of the National Institutes of Health genetically heterogeneous rat stock. , 1984, Alcoholism, clinical and experimental research.

[36]  J Piiper,et al.  Model for capillary-alveolar equilibration with special reference to O2 uptake in hypoxia. , 1981, Respiration physiology.

[37]  D. Hartl,et al.  Principles of population genetics , 1981 .

[38]  E R Weibel,et al.  Design of the mammalian respiratory system. VII. Scaling mitochondrial volume in skeletal muscle to body mass. , 1981, Respiration physiology.

[39]  C. Tipton,et al.  Maximum oxygen consumption of rats and its changes with various experimental procedures. , 1979, Journal of applied physiology: respiratory, environmental and exercise physiology.

[40]  H. Grüneberg,et al.  Introduction to quantitative genetics , 1960 .

[41]  R. Hepple,et al.  Skeletal muscle: microcirculatory adaptation to metabolic demand. , 2000, Medicine and science in sports and exercise.

[42]  C. Bouchard,et al.  Familial aggregation of V ˙ O 2max response to exercise training: results from the HERITAGE Family Study , 1999 .

[43]  H. Groth,et al.  Determinants of VO2max in rats after high-intensity sprint training. , 1989, Journal of applied physiology.