Time course changes of BAR.
The time course of change in BAR is presented in Figure 2. BAR of the trained arm improved 30% by the second week of training (2.9 ± 1.5 at baseline vs 3.8 ± 1.7 at week 2, P = 0.02) and remained statistically significant compared with pretraining values for the remainder of the intervention (P < 0.05). BAR continued to increase from week 2 to week 4 (maximal improvement 45%), but the changes were not significant from week 2. No significant changes in BAR were noted in the untrained arm during the intervention.
Effects of exercise training on blood flow and shear rate.
Estimates of blood flow at rest and immediately after cuff occlusion for the trained and control arms are presented in Table 3. In addition, the estimated peak wall shear rate immediately after cuff occlusion and the relevant shear stimulus (AUC) are also shown in Table 3. No significant differences in flow and the shear values were observed between arms before training. Estimates of blood flow during reactive hyperemia were significantly higher in the trained arm at weeks 3 and 4 compared with pretraining values. No such changes were noted for the control arm. Peak wall shear rates also increased significantly by week 3 in the trained arm. In contrast, the relevant shear stimulus did not change significantly in the trained arm across the training period but was significantly higher compared with that in the control arm at weeks 2 to 4.
Finally, Pearson product moment correlations revealed significant relationships between the average relevant shear stimulus (AUC) and BAR (r = 0.76, P < 0.001) in either arm across all visits.
The purpose of this study was to examine the influence of a unilateral exercise training protocol on BAR in a group of older men. Four weeks of exercise training resulted in a∼45% increase in BAR of the trained arm only. A significant improvement was observed by the end of the second week of training and was maintained throughout the duration of the study. This finding indicates the vasculature's ability to respond favorably to an exercise stimulus is preserved in individuals in their 9th and 10th decades of life. Moreover, BAR adaptations occur relatively early after the onset of training and are observed before any alterations in the stimulus for dilation.
Unilateral response to exercise training.
Before training, brachial artery resting diameters, blood flow, and peak wall shear rates were similar to data from the Louisiana Healthy Aging study (36). The BAR observed in the present study ranged from 2.9% to 4.2%, which is also quite similar to what has been reported in larger investigations of older healthy adults (6,14) including our own (36). Typically, when comparing these findings to younger age groups, BAR is blunted, thus suggesting an age-related decline in the endothelium-dependent function (15,36).
The improvement in BAR in response to exercise training is also in agreement with others (8,37) who studied adults between the age of 50 and 76 yr. Desouza et al. (8) reported a 30% improvement in acetylcholine-induced forearm blood flow in response to 3 months of aerobic exercise, which consisted mostly of walking. More recently, Wray et al. (37) observed a significant improvement in BAR after 6 wk of single-leg knee extensor training. Collectively, the mean age of the participants in the above studies was 63 yr. Thus, the present findings extend our current knowledge of exercise training effects on vascular function to men in their 9th and 10th decades of life. Importantly, the observed changes, in the present study, were quite consistent, in that, all trained arms increased the absolute change in vessel diameter after forearm occlusion. In contrast, there were no improvements in any of the control arms during the same period.
Whereas the present study was not designed to address the underlying mechanisms for change, the findings do provide direct evidence of the plasticity of the vasculature, even in those in their 9th and 10th decades of life. It is hypothesized (17) that the repetitive shear stress associated with muscle contractions signals formation of beneficial endothelial cell phenotype, including increased nitric oxide production, endothelial nitric oxide synthase (eNOS), prostacyclin (PGI2), antioxidant defenses, and a reduction in reactive oxygen species, adhesion molecules, and vasoconstriction factors (e.g., endothelin 1). That said, we acknowledge that the improvement in BAR may, in part, be the result of a change in the trigger for vasodilation. Indeed, both the reactive hyperemic flow response and estimated peak shear rate (23) were significantly higher at week 4 in the trained arm compared with those in the pretraining measures. This increase in postocclusion blood flow after training has been reported previously (2,18,25,37). We speculate that this increase may be secondary to regional adaptations including enhanced endothelial-dependent resistance vessel function (19) and changes in microcirculation (28,34). However, it is important to acknowledge that recent evidence indicates (24) that the continued shear stimulus imposed on the vessel wall before peak diameter response ("relevant" shear stimulus) is a more accurate predictor of BAR than the peak shear stimulus. A lack of change in relevant shear rate (AUC) in the trained arm, in the present study, suggests that the trigger for BAR did not change, yet the reactivity did. This finding would favor a change in the mechanisms underlying BAR.
Time course of change in BAR.
Hypothesizing that handgrip training would indeed result in a significant increase in BAR, a second objective was to examine the time course of these vascular adaptations. Evidence for rapid changes in vasoreactivity with training were first reported by Wang et al. (32) who found an increase in vasodilatory responses in the circumflex coronary artery of dogs, owing to a greater release of endothelial-derived NO, after 7 d of exercise training. Studies conducted in our laboratory have confirmed these rapid changes in vasodilatory function in humans (1,2). For example, Allen et al. (1) observed a significant change in BAR after 4 d of handgrip training in young men using a similar training protocol. The findings from the current investigation indicate a statistically significant improvement in the BAR of the trained arm after 8 d of training. Importantly, the change in BAR after only 8 d of training occurred without significant changes in the trigger for dilation compared with pretraining. Thus, the present findings seem to confirm previous studies that indicate that vascular adaptations occur relatively quickly after the onset of training.
It is worth noting that the improvement in BAR was of lesser magnitude and slower in onset than our previous observations in young men (1). The reason for the slower response and lower magnitude in improvement in the current study is not clear but may include both protocol-related differences and/or physiologic differences between young and old. About protocol differences, it is evident that although the relative intensity of the exercise training was the same (60% MVC) between studies, the older men trained at a lower absolute workload (∼20 kg in the old vs 26 kg in the young), perhaps suggesting the importance of training volume rather than merely exercise intensity. Thus, further research is needed to determine the threshold of training volume needed to elicit vascular adaptations. However, it is important to appreciate that the strength gains in the trained arm in the present study are nearly identical to those reported by Allen et al. (1) (6.3% increase in handgrip strength).
A second factor that may have influenced the magnitude of the training response in the present study is the size of the brachial artery diameter. Typically, the size of the brachial artery diameter is inversely related to BAR (5,14). Moreover, brachial artery diameter increases with age (14), perhaps due to structural modifications or increased resistance in smaller arterioles downstream. Thus, a lower magnitude of response to training could certainly be a consequence of the pretraining conditions. Specifically, the pretraining average brachial artery diameter in the present study (4.47mm) is much higher than what Allen et al. (1) reported (3.38 mm), perhaps suggesting that older individuals are closer to their physiologic ceiling. However, the lower magnitude of response in this study could certainly be the consequence of age-related changes within the biological systems that underlie the vascular adaptations to exercise training. This hypothesis has been advanced by others (9) who report that nonfrail octogenarians who undergo strenuous endurance exercise experience attenuated adaptations in V˙O2max and insulin action compared with those between the ages of 60 and 70 yr. Our current findings suggest that this blunted adaptation may apply to the vasculature as well. Clearly, future efforts should focus on understanding the attenuation in the capacity to adapt to training in the elderly, as this may lead to determining the optimal mode and volume (intensity, duration, frequency) of exercise needed to stimulate physiological systems in the elderly.
We have previously discovered that vascular health is associated with measures of physical function in older adults (36). These prior findings fit "the disablement process" (31) and suggest that lower physical function may in part be the consequence of some defect in peripheral vascular function, which contributes to functional limitations and ultimately contribute to loss of dependence and disability in the elderly. The apparent specificity of the observed changes, within the present study, emphasizes the need for a well-rounded exercise program as outlined in the American College of Sports Medicine's 1998 position statement. Interestingly, findings from studies in heart failure and peripheral arterial disease suggest that training-induced vascular improvements may contribute to improved heart function and aerobic capacity (12,13) and prognosis. Given our current observations, it seems that exercise training is an effective strategy to improve vascular function even in individuals in their 10th decade of life. Future efforts should focus on how/if exercise-induced improvements in vascular function contribute to the preservation of functional ability and independence in the elderly.
In conclusion, a localized short-term exercise program resulted in significant improvements in BAR of the trained arm of elderly men compared with the control arm. Furthermore, the findings indicate a statistical significant increase in BAR at the end of the second week of training, despite a similar trigger for dilation versus pretraining. The improved BAR was maintained throughout the remainder of the training period but may have, in part, been aided by a larger vasodilatory trigger toward the end of the study. These findings indicate the ability of the vasculature to respond favorably to an exercise stimulus even in individuals in their 9th and 10th decades of life.
The authors thank Daniel Credeur, Rachana Vasaiwala, and Kim Landry for their dedication, commitment, and technical support.
This research was supported by a grant from the National Institute on Aging (1 P01 AG022064) (S.M. Jazwinski).
Louisiana Healthy Aging Study: Meghan B. Allen, B.S.; Arturo M. Arce-Esquivel, M.D.; Mark A. Batzer, Ph.D.; Lauri Byerley, Ph.D.; Cathy Champagne, Ph.D.; Katie E. Cherry, Ph.D.; M. Elaine Cress, Ph.D.-Consultant; James P. DeLany, Ph.D.; Jenny Y. Denver, M.S.; Andy Deutsch, Ph.D.; Devon A. Dobrosielski, M.S.; Marla J. Erwin, M.A.; Elizabeth T. Fontham, Ph.D.; Madlyn Frisard, Ph.D.; Paula Geiselman, Ph.D.; Lindsey Goodwin; Tiffany Hall; Scott W. Herke, Ph.D.; Jennifer Hayden, M.S.; Kristi Hebert; Hui-Chen Hsu, Ph.D.; S.Michal Jazwinski, Ph.D.; Sangkyu Kim, Ph.D.; Beth G. Kimball, B.S.; Kim Landry; Daniel LaVie; Matthew Leblanc; Li Li, M.D.; Hui-Yi Lin, Ph.D., M.S.P.H.; Kay Lopez, D.S.N.; John D. Mountz, M.D., Ph.D.; Emily A. Olinde, M.A.; Kim B. Pedersen, Ph.D.; Eric Ravussin, Ph.D.; Paul Remedios; Yolanda Robertson, N.P.; Jennifer Rood, Ph.D.; Henry Rothschild, M.D., Ph.D.; Erin Sandifer; Beth Schmidt, M.S.; Robert Schwartz, M.D.-Consultant; Donald K. Scott, Ph.D.; Jennie L. Silva, M.A.; L. Joseph Su, Ph.D., M.P.H.; Jessica Thomson, Ph.D.; Crystal Traylor, A.P.R.N., M.S.N., W.H.N.P.; Cruz Velasco-Gonzalez, Ph.D.; Jerilyn A. Walker, MS.; David A. Welsh, M.D.; Michael A. Welsch, Ph.D.; Pili Zhang, Ph.D. (Louisiana State University, Baton Rouge; Pennington Biomedical Research Center, Baton Rouge; Louisiana State University Health Sciences Center, New Orleans; University of Alabama, Birmingham).
The results of the present study do not constitute endorsement by ACSM.
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Keywords:©2009The American College of Sports Medicine
BRACHIAL ARTERY REACTIVITY; OLDER ADULTS; VASCULAR PLASTICITY; SHEAR RATE