Effects of aging on microvascular oxygen pressures in rat skeletal muscle

Behnke, Brad J.; Delp, Michael D.; Dougherty, Patrick J.; Musch, Timothy I.; Poole, David C.

doi:10.1016/j.resp.2004.12.009

Cited by 90 publications

(115 citation statements)

References 74 publications

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“…However, in our analysis, we average data into 5-or 10-s time bins to reduce variability in the profiles that may obscure any overshoot that might exist during the exercise transient. Also, Poole and colleagues (5,6,11,27) use an exposed, in situ animal muscle preparation to study microvascular PO 2 , whereas we study NIRS-derived HHb changes measured on the skin surface above the quadriceps muscle during human exercise, where the fidelity of the response may not be as great. In general the NIRS-derived HHb signal adapts with an "exponential-like" profile that we find can be fit adequately using a monoexponential model (see Fig.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of O₂uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

MacPhee

Shoemaker²,

Paterson³

et al. 2005

Journal of Applied Physiology

110

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(SD 4)] performed repetitions (6 -8) of twolegged, moderate-intensity, knee-extension exercise during two separate protocols that included step transitions from 3 W to 90% estimated lactate threshold ( L) performed as a single step (S3) and in two equal steps (S1, 3 W to ϳ45% L; S2, ϳ45% L to ϳ90% L). The time constants ( ) of pulmonary oxygen uptake (V O2), leg blood flow (LBF), heart rate (HR), and muscle deoxygenation (HHb) were greater (P Ͻ 0.05) in S2 ( V O2, ϳ52 s; LBF, ϳ 39 s; HR, ϳ42 s; HHb, ϳ33 s) compared with S1 ( V O2, ϳ24 s; LBF, ϳ21 s; HR, ϳ21 s; HHb, ϳ16 s), while the delay before an increase in HHb was reduced (P Ͻ 0.05) in S2 (ϳ14 s) compared with S1 (ϳ20 s). The V O2 and HHb amplitudes were greater (P Ͻ 0.05) in S2 compared with S1, whereas the LBF amplitude was similar in S2 and S1. Thus the slowed V O2 response in S2 compared with S1 is consistent with a mechanism whereby V O2 kinetics is limited, in part, by a slowed adaptation of blood flow and/or O2 transport when exercise was initiated from a baseline of moderate-intensity exercise.oxygen uptake kinetics; femoral arterial blood flow kinetics; Doppler ultrasound; knee-extension exercise; near-infrared spectroscopy ACCOMPANYING A RISE IN EXERCISE intensity, there is a challenge to increase the rate of oxidative phosphorylation to meet the new metabolic demand of the working muscle. To meet this demand, the respiratory and cardiovascular systems must adapt in a coordinated manner to transport O 2 from the atmosphere to the mitochondria of the exercising muscle, thus allowing oxidative phosphorylation to proceed at the required rate. Pulmonary O 2 uptake (V O 2 ) kinetics is an index of the overall efficiency and conditioning of these integrated systems and can provide pertinent information with regard to the various mechanisms regulating O 2 delivery and O 2 utilization by skeletal muscle during exercise.Recently, it was reported (8) that, for a given absolute increase in work rate (WR), the adaptation of V O 2 during leg-cycling exercise was slower and the gain (G) (i.e., ⌬V O 2 / ⌬WR) was greater when exercise was initiated in the upper compared with the lower regions of the moderate-intensity exercise domain. These observations agree with those of Hughson and Morrissey (22,23) and DiPrampero et al. (13), but differ from those of DiPrampero et al. (12) and Diamond et al.(10), who reported either a faster or similar adaptation, respectively, when comparing exercise initiated from either prior moderate-intensity exercise or rest.Brittain et al. (8) attributed the slowing of V O 2 kinetics in the upper region of the moderate-intensity domain to the bioenergetic properties of the newly recruited motor units, which were assumed to be less efficient (i.e., greater O 2 or ATP cost per contraction) with a more slowly adapting V O 2 response than those motor units recruited initially at exercise onset from rest or very light exercise (i.e., lower region of the moderateintensity domain). Hughson and Morrissey (22,23), however, suggested that the sl...

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Section: Discussionmentioning

confidence: 99%

Kinetics of O₂uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

MacPhee

Shoemaker²,

Paterson³

et al. 2005

Journal of Applied Physiology

110

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“…It is also pertinent to note that the dietary intervention in the present study was short-term. Longer-term NO 3 Ϫ supplementation may be required to enhance vascular structure and function (68), which may, in turn, improve the matching of O 2 delivery to metabolic rate (7,18) and enhance metabolic control. Future studies should consider the possible benefits of longer-term NO 3 Ϫ supplementation in senescent subjects with greater physical and cognitive impairment.…”

Section: Experimental Considerationsmentioning

confidence: 99%

“…For instance, the ability to increase cardiac output (45) and skeletal muscle blood flow (80) during exercise is attenuated with increasing age. Moreover, the distribution of blood flow in the microcirculation, capillary density, and capillary hemodynamics (7,8,18,30,59,60,65), as well as mitochondrial volume density and oxidative function (15,16) are compromised with aging. There is evidence that V O 2 kinetics in the transition from a lower to a higher metabolic rate is slowed in older compared with younger adults (3,14,22) and that this may be related to a limitation in muscle O 2 delivery (66).…”

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confidence: 99%

Effects of short-term dietary nitrate supplementation on blood pressure, O₂uptake kinetics, and muscle and cognitive function in older adults

Kelly

Fulford

Vanhatalo

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

206

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AM. Effects of shortterm dietary nitrate supplementation on blood pressure, O 2 uptake kinetics, and muscle and cognitive function in older adults. Am J Physiol Regul Integr Comp Physiol 304: R73-R83, 2013. First published November 21, 2012 doi:10.1152/ajpregu.00406.2012 Ϫ ) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults. We investigated whether these effects might also be evident in older adults. In a double-blind, randomized, crossover study, 12 healthy, older (60 -70 yr) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice (BR; 2 ϫ 70 ml/day, ϳ9.6 mmol/day NO 3 Ϫ ) or a nitrate-depleted beetroot juice placebo (PL; 2 ϫ 70 ml/day, ϳ0.01 mmol/day NO 3 Ϫ ). Before and after the intervention periods, resting blood pressure and plasma [nitrite] were measured, and subjects completed a battery of physiological and cognitive tests. Nitrate supplementation significantly increased plasma [nitrite] and reduced resting systolic (BR: 115 Ϯ 9 vs. PL: 120 Ϯ 6 mmHg; P Ͻ 0.05) and diastolic (BR: 70 Ϯ 5 vs. PL: 73 Ϯ 5 mmHg; P Ͻ 0.05) blood pressure. Nitrate supplementation resulted in a speeding of the V O2 mean response time (BR: 25 Ϯ 7 vs. PL: 28 Ϯ 7 s; P Ͻ 0.05) in the transition from standing rest to treadmill walking, although in contrast to our hypothesis, the O 2 cost of exercise remained unchanged. Functional capacity (6-min walk test), the muscle metabolic response to low-intensity exercise, brain metabolite concentrations, and cognitive function were also not altered. Dietary nitrate supplementation reduced resting blood pressure and improved V O2 kinetics during treadmill walking in healthy older adults but did not improve walking or cognitive performance. These results may have implications for the enhancement of cardiovascular health in older age.nitrate; nitrite; nitric oxide; blood pressure; exercise performance; cognitive performance; O2 uptake kinetics THE BENEFICIAL EFFECTS OF a vegetable-rich diet upon cardiovascular health (27) and longevity (79) have been well described. These positive effects have been attributed, in part, to inorganic nitrate (NO 3 Ϫ ), which is particularly rich in leafy greens and beetroot. The NO 3 Ϫ anion itself is inert, and any biological effects are likely to be the result of its conversion to the nitrite anion (NO 2 Ϫ ) in the mouth via facultative anaerobic bacteria on the surface of the tongue (25). When swallowed, NO 2 Ϫ can be further converted into nitric oxide (NO) (9), but it is clear that some NO 2 Ϫ enters the circulation. The subsequent reduction of NO 2 Ϫ to NO and other reactive nitrogen intermediates is facilitated in hypoxia (11). The production of NO via nitric oxide synthase (NOS) is impaired in hypoxia and, thus, it has been proposed that the NO 3 Ϫ -NO 2 Ϫ -NO pathway represents a complementary system for NO generation across a wide range of redox states (53). NO is an essential physiological signaling molecule with numerous functions in...

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“…Heart rate kinetics, an index of bulk blood flow, are slowed during the transition to exercise (12,13,51), while muscle (conduit artery) blood flow (39,43,44) is lower and its distribution within muscle is altered (away from more oxidative to more glycolytic fibers), thereby lowering microvascular PO 2 and diffusive O 2 delivery to active muscle (3,11,39,43,49). These results, from both human and rat work, suggest an impaired O 2 availability, which could delay the activation of oxidative phosphorylation and V O 2p kinetics during the transition to exercise.…”

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confidence: 99%

Prior heavy exercise elevates pyruvate dehydrogenase activity and muscle oxygenation and speeds O₂uptake kinetics during moderate exercise in older adults

Gurd

Peters²,

Heigenhauser³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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(V O2p) kinetics during the transition to moderate-intensity exercise is slowed in older compared with younger adults; however, this response is faster following a prior bout of heavy-intensity exercise. We have examined V O2p kinetics, pyruvate dehydrogenase (PDH) activation, muscle metabolite contents, and muscle deoxygenation in older adults [n ϭ 6; 70 Ϯ 5 (67-74) yr] during moderate-intensity exercise (Mod 1) and during moderate-intensity exercise preceded by heavy-intensity warm-up exercise (Mod2). The phase 2 V O2p time constant (V O2p) was reduced (P Ͻ 0.05) in Mod2 (29 Ϯ 5 s) compared with Mod1 (39 Ϯ 14 s). PDH activity was elevated (P Ͻ 0.05) at baseline prior to Mod2 (2.1 Ϯ 0.6 vs. 1.2 Ϯ 0.3 mmol acetyl-CoA ⅐ min Ϫ1 ⅐ kg wet wt Ϫ1 ), and the delay in attaining end-exercise activity was abolished. Phosphocreatine breakdown during exercise was reduced (P Ͻ 0.05) at both 30 s and 6 min in Mod2 compared with Mod1. Near-infrared spectroscopyderived indices of muscle oxygenation were elevated both prior to and throughout Mod2, while muscle deoxygenation kinetics were not different between exercise bouts consistent with elevated perfusion and O2 availability. These results suggest that in older adults, faster V O2p kinetics following prior heavy-intensity exercise are likely a result of prior activation of mitochondrial enzyme activity in combination with elevated muscle perfusion and O2 availability. V O2 kinetics; ageing; pyruvate dehydrogenase; phosphocreatine DURING THE TRANSITION TO moderate-intensity exercise there is a delay in the full activation of mitochondrial oxidative phosphorylation, as estimated by pulmonary O 2 uptake (V O 2p ) kinetics (2, 21, 38), such that it can take several minutes before a new steady-state in aerobic ATP production meets ATP demand (55). It has been suggested that this delay is a result of either a slowed activation of oxidative enzymes and provision of substrates other than O 2 to the mitochondrial tricarboxylic acid (TCA) cycle and electron transport chain (ETC) (e.g., acetyl-CoA; NADH) (20,42), an inadequate supply of O 2 during the transition to exercise (33), or the interaction between these two (22,54). In older compared with young adults, V O 2p kinetics, reflecting the adaptation of muscle O 2 utilization, are slowed during the transition to moderate-and heavyintensity exercise (1, 5, 9, 11). Whether this slower response in older adults is a result of an increased sluggishness in activating muscle enzymes and providing oxidative substrate (occasionally referred to as metabolic inertia), an impaired O 2 delivery, or both has not been established.Recently, we demonstrated that the activation of the mitochondrial enzyme pyruvate dehydrogenase (PDH) was attenuated during the transition to moderate-intensity exercise in older compared with young adults (23). To our knowledge this is the first direct demonstration, in older adults, that the activation of a rate-limiting oxidative enzyme is impaired during the transition to exercise. These data suggest a potential rol...

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Effects of aging on microvascular oxygen pressures in rat skeletal muscle

Cited by 90 publications

References 74 publications

Kinetics of O₂uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

Kinetics of O₂uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

Effects of short-term dietary nitrate supplementation on blood pressure, O₂uptake kinetics, and muscle and cognitive function in older adults

Prior heavy exercise elevates pyruvate dehydrogenase activity and muscle oxygenation and speeds O₂uptake kinetics during moderate exercise in older adults

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Effects of aging on microvascular oxygen pressures in rat skeletal muscle

Cited by 90 publications

References 74 publications

Kinetics of O2uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

Kinetics of O2uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

Effects of short-term dietary nitrate supplementation on blood pressure, O2uptake kinetics, and muscle and cognitive function in older adults

Prior heavy exercise elevates pyruvate dehydrogenase activity and muscle oxygenation and speeds O2uptake kinetics during moderate exercise in older adults

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Kinetics of O₂uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

Kinetics of O₂uptake, leg blood flow, and muscle deoxygenation are slowed in the upper compared with lower region of the moderate-intensity exercise domain

Effects of short-term dietary nitrate supplementation on blood pressure, O₂uptake kinetics, and muscle and cognitive function in older adults

Prior heavy exercise elevates pyruvate dehydrogenase activity and muscle oxygenation and speeds O₂uptake kinetics during moderate exercise in older adults