mRNA expression of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and hypoxia-inducible factor (HIF) subunits HIF-1α and HIF-1β in human skeletal muscle was studied during endurance exercise at different degrees of oxygen delivery. Muscle biopsies were taken before and after 45 min of one-legged knee-extension exercise performed under conditions of nonrestricted or restricted blood flow (∼15–20% lower) at the same absolute workload. Exercise increased VEGF mRNA expression by 178% and HIF-1β by 340%, but not HIF-1α and FGF-2. No significant differences between the restricted and nonrestricted groups were observed. The exercise-induced increase in VEGF mRNA was correlated to the exercise changes in HIF-1α and HIF-1β mRNA. The changes in VEGF, HIF-1α, and HIF-1β mRNAs were correlated to the exercise-induced increase in femoral venous plasma lactate concentration. It is concluded that 1) VEGF but not FGF-2 gene expression is upregulated in human skeletal muscle by a single bout of dynamic exercise and that there is a graded response in VEGF mRNA expression related to the metabolic stress and 2) the increase in VEGF mRNA expression correlates to the changes in both HIF-1α and HIF-1β mRNA.
In the present article, three scales developed by Borg are compared on bicycle ergometer work. In the first study, comparing the Borg Ratings of Perceived Exertion (RPE) and Category scales with Ratio properties (CR10) scales, 40 healthy subjects (12 men and eight women for each scale) with a mean age of about 30 years (SD approximately 6) participated. A work-test protocol with step-wise increase of work loads every minute was used (20 W increase for men and 15 W for women). Ratings and heart rates (HRs) were recorded every minute and blood lactates every third minute. Data obtained with the RPE scale were described with linear regressions, with individual correlations of about 0.98. Data obtained with the CR10 scale could also be described by linear regressions, but when described by power functions gave exponents of about 1.2 (SD approximately 0.4) (with one additional constant included in the power function). This was significantly lower than the exponent of between 1.5 and 1.9 that has previously been observed. Mean individual correlations were 0.98. Blood lactate concentration grew with monotonously increasing functions that could be described by power functions with a mean exponent of about 2.6 (SD approximately 0.6) (with two additional constants included in the power functions). In the second study, where also the more recently developed Borg CR100 scale (centiMax) was included, 24 healthy subjects (12 men and 12 women) with a mean age of about 29 years (SD approximately 3) participated in a work test with a step-wise increase of work loads (25 W) every third minute. Ratings and HRs were recorded. RPE values were described by linear regressions with individual correlations of about 0.97. Data from the two CR scales were described by power functions with mean exponents of about 1.4 (SD approximately 0.5) (with a-values in the power functions). Mean individual correlations were about 0.98. In both studies, a tendency for a deviation from linearity between RPE values and HRs was observed. The obtained deviations from what has previously been obtained for work of longer duration (4-6 min) points to a need for standardization of work-test protocols and to the advantage of using CR scales.
SUBMARY1. The effects of altered tissue temperature on muscle metabolism during successive isometric contractions, sustained to fatigue, have been studied in the quadriceps muscle of man by combining biochemical analyses of metabolites in needle biopsy samples with measurements of endurance time with a force of 2/3 maximum voluntary contraction. Fatigue and recovery were observed repeatedly in a series of seven contractions at intervals of 20 sec, following immersion of the test leg in water at 12, 26 or 440 C for 45 min. Muscle temperatures corresponding to these water temperatures were 22-5, 32-6 and 38 6°C respectively.2. Increased levels of several glycolytic intermediates at rest in the heated muscle suggested an increased rate of glycolysis. ATP and phosphoryl creatine were lower at the end of the first contraction and the calculated rate of ATP utilization (including the contribution from anaerobic glycolysis) was highest in the heated nuscle.3. Significantly shorter endurance times were found for the heated muscle. These could not be attributed to depletion of local energy resources in muscle. Fatigue may be due to a reduction in the rate of regeneration of ATP from anaerobic glycolysis below that needed to maintain the contraction force. Lower values for the ratio of fructose 1,6-diphosphate: fructose 6-phosphate at the end of contractions, particularly at the highest temperature, are compatible with the hypothesis that there is partial inhibition of the rate controlling enzyme phosphofructokinase, possibly due to the accumulation of hydrogen ions in muscle.
To compare two situations with similar magnitudes of mitochondrial substrate flux but different blood oxygen contents, one-legged training was employed. Ten healthy subjects trained one leg under normobaric conditions and the other under hypobaric conditions. At each session the subjects trained each leg for 30 min. The absolute work intensity was the same for both legs and was chosen to correspond to 65% of the average (right and left) pretraining one-legged maximal work capacity. There were three to four training sessions per week for 4 wk. Muscle biopsies from each leg were taken before and after training and analyzed for fiber types, capillaries, myoglobin, and oxidative and glycolytic enzymes. The most striking finding was a greater increase of citrate synthase activity under hypobaric conditions than under normobaric conditions. In addition, the myoglobin content increased in the leg trained under hypobaric conditions, whereas it tended to decrease in the normobarically trained leg. Because both legs were trained at the same intensity, the oxygen turnover and the substrate flux through the carboxylic acid cycle and the respiratory chain must have been of similar magnitude. Thus a difference in substrate flux is less likely to have caused the differences in enzyme activities and myoglobin content between training under normobaric and hypobaric conditions. Instead, the stimulus seems to be related to the blood oxygen content or tension.
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