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Biomedical subjects

David N Proctor

Publications and source records attributed to David N Proctor.

13 recordsLinked to original sources
PubMed2005

Age and regional specificity of peak limb vascular conductance in women.

The influence of age on limb vasodilator capacity in women is unclear. The objectives of this study were to characterize and compare age-associated changes in forearm and calf peak vascular conductance (VC(peak); a functional index of arterial structure) in women and to identify physiological characteristics predictive of variation in limb-specific VC(peak). Peak conductance (plethysmographic flow/mean arterial pressure), VC(peak) of the forearm (forearm VC(peak)), and calf (calf VC(peak)) after 10 min of arterial occlusion were measured in 58 healthy, normally active women aged 21-79 yr. Aerobic capacity (cycle peak oxygen uptake), arterial health (pulse-wave velocity, ankle-brachial index), total cholesterol, limb-specific tissue composition (dual-energy X-ray absorptiometry), and isometric strength (handgrip, plantar flexion) were also assessed. The relative decline in calf VC(peak) with age (-6.8% per decade, P < 0.001) was greater than the forearm (-4.4% per decade, P = 0.004), in contrast to results previously reported for men (forearm decline > calf decline). Limb VC(peak) per kilogram muscle declined with age in the calf (-6.0% per decade; P = 0.002), but not the forearm (P = 0.12). Age, cholesterol, and regional tissue composition were significant predictors of peak conductance in both limbs; however, age was a stronger predictor of peak conductance in the calf. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in women, but the magnitude of this effect is region specific. Further research will be required to determine whether the decline in lower extremity vasodilator capacity with age explains diminished exercising leg vasodilation in older women.

Adult↗
PubMed2005

Heterogeneous vasodilator responses of human limbs: influence of age and habitual endurance training.

Forearm endothelium-dependent vasodilation is impaired with age in sedentary, but not endurance-trained, men. The purpose of this investigation was to determine whether these age- and physical activity-related differences in endothelium-dependent vasodilation also occur in the leg. Brachial and common femoral arterial blood flow were measured with Doppler ultrasound during increasing doses of acetylcholine (1, 4, and 16 microg.100 ml limb tissue(-1).min(-1)), substance P (8, 31, and 125 pg.100 ml limb tissue(-1).min(-1)), and sodium nitroprusside (0.063, 0.25, and 1 microg.100 ml limb tissue(-1).min(-1)) in 23 healthy men (8 younger sedentary, 8 older sedentary, and 7 older endurance trained). Increases in forearm blood flow to the highest dose of acetylcholine and sodium nitroprusside were smaller (P < 0.05) in older sedentary (841 +/- 142%, 428 +/- 74%) compared with younger sedentary (1,519 +/- 256%, 925 +/- 163%) subjects. Similarly, increases in forearm blood flow to sodium nitroprusside (1 microg.100 ml limb tissue(-1).min(-1)) were smaller (P < 0.05) in older endurance-trained (505 +/- 110%) compared with younger sedentary (925 +/- 163%) subjects. In contrast, no differences in leg blood flow responses to intra-arterial infusions of acetylcholine, substance P, or sodium nitroprusside were noted between subject groups. These results demonstrate that 1) acetylcholine- and sodium nitroprusside-induced vasodilation are attenuated in the forearm vasculature and preserved in the leg vasculature of older sedentary subjects and 2) sodium nitroprusside-induced vasodilation remains attenuated in the forearm vasculature of healthy older endurance-trained men but preserved in the leg vasculature of these men.

Acetylcholine↗
PubMed2005

Changes in myosin heavy chain mRNA and protein expression in human skeletal muscle with age and endurance exercise training.

Aging is associated with reduced muscle strength and atrophy of type II muscle fibers. Muscle fiber type and contractile function are primarily determined by myosin heavy chain (MHC) isoforms. There are few data available on the effects of aging on MHC isoform expression in humans. In the present study, we tested the hypothesis that MHC isoform protein composition and mRNA abundance would favor a fast-to-slow isoform shift with aging and in response to endurance exercise training. Muscle biopsies were obtained from previously sedentary, healthy men and women, aged 21-87 yr before (n = 77) and after (n = 65) 16 wk of bicycle training (up to 45 min at 80% peak heart rate, 3-4 days/wk). At baseline, MHC I mRNA was unchanged with age, whereas IIa and IIx declined by 14 and 10% per decade, respectively (P < 0.001). MHC IIa and IIx protein declined by 3 and 1% per decade with a reciprocal increase in MHC I (P < 0.05). After training, MHC I and IIa mRNA increased by 61 and 99%, respectively, and IIx decreased by 50% (all P < 0.001). The increase in MHC I mRNA was positively associated with age, whereas the changes in MHC IIa and IIx mRNA were similar across age. MHC I protein increased by 6% and was positively related to age, whereas IIx decreased by 5% and was inversely related to age. These results suggest that the altered expression of MHC isoforms with aging is transcriptionally regulated. In response to endurance exercise, regulation of MHC isoform transcripts remains robust in older muscle, but this did not result in corresponding changes in MHC protein expression.

Adaptation, Physiological↗
PubMed2005

Blood flow to exercising limbs varies with age, gender, and training status.

Understanding the effects of physiological aging on blood flow to active skeletal muscle and its regulation during exercise has important functional, hemodynamic, and metabolic implications for our rapidly expanding elderly population. During peak exercise involving a large muscle mass, blood flow to the legs is lower in healthy older compared to younger persons; this results from central (reduced cardiac output) and peripheral (reduced leg vascular conductance) limitations. There is considerable variability in the literature concerning age-related changes in leg blood flow during submaximal exercise, with reports of similar or reduced leg blood flow and vascular conductance in older vs. younger subjects depending on the exercise intensity and the gender and training status of the subjects. However, all the studies involving non-endurance-trained subjects are consistent in that older subjects achieve the requisite leg blood flow at higher arterial perfusion pressures than young subjects, suggesting altered local vasoregulatory mechanisms with aging. Although the nature of these age-related alterations is poorly understood, we have preliminary evidence for augmented sympathetic vasoconstrictor responsiveness in the legs of older men during exercise, and blunted leg vasodilator responsiveness in older women. Systematic research will be needed in order to define the central and local mechanisms underlying these age- and gender-specific differences in muscle vascular responsiveness. Such information will be important for designing future interventions aimed at improving muscle blood supply and functional capacity in older persons.

Aging↗
PubMed2004

Age and regional specificity of peak limb vascular conductance in men.

Because of methodological variation in previous studies, age-associated changes in peak limb vascular conductance (VC(peak); a functional index of arterial structure) and its determinants remain poorly defined. The objectives of this study were to describe and compare age-associated changes in peak forearm and calf conductance across a broad age range and to identify physiological characteristics that are predictive of variation in limb-specific VC(peak). Peak conductance (plethysmographic flow/brachial mean arterial pressure) of the forearm (forearm VC(peak)) and calf (calf VC(peak)) after 10 min of arterial occlusion was measured twice in 68 healthy, normally active men aged 20-79 yr. Aerobic capacity (cycle peak oxygen consumption), arterial health (ankle-brachial index, pulse wave velocity), and limb-specific measures of muscle mass (dual-energy X-ray absorptiometry) and isometric strength (grip, plantar flexion) were also assessed. The relative decline in forearm VC(peak) with age (-6.6% per decade; P < 0.001) was greater than the decline in calf VC(peak) (-3.4% per decade; P = 0.004). Limb VC(peak) per kilogram of muscle declined with age in the forearm (-3.8% per decade; P = 0.004) but not in the calf (P = 0.35). Age, Vo(2 peak), and regional muscle mass were significant predictors of peak conductance in both limbs; however, these predictors explained considerably less variance in the calf than in the forearm. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in men, but the magnitude of this effect is reduced in the calf relative to the forearm. This could reflect regional differences in habitual muscle use with aging in normally active men.

Adult↗
PubMed2004

Different vasodilator responses of human arms and legs.

Forearm vascular responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators have been thoroughly characterized in humans. While the forearm is a well-established experimental model for studying human vascular function, it is of limited consequence to systemic cardiovascular control owing to its small muscle mass and blood flow requirements. In the present study we determined whether these responses could be generalized to the leg. Based upon blood pressure differences between the leg and arm during upright posture, we hypothesized that the responsiveness to endothelium-dependent vasodilators would be greater in the forearm than the leg. Brachial and femoral artery blood flow (Q, ultrasound Doppler) at rest and during intra-arterial infusions of endothelium-dependent (acetylcholine and substance P) and -independent (sodium nitroprusside) vasodilators were measured in eight healthy men (22-27 years old). Resting blood flows in the forearm before infusion of acetylcholine, substance P or sodium nitroprusside were 25 +/- 4, 30 +/- 7 and 29 +/- 5 ml min(-1), respectively, and in the leg were 370 +/- 32, 409 +/- 62 and 330 +/- 30 ml min(-1), respectively. At the highest infusion rate of acetylcholine (16 microg (100 ml tissue)(-1) min(-1)) there was a greater (P < 0.05) increase in Q to the forearm (1864 +/- 476%) than to the leg (569 +/- 86%). Similarly, at the highest infusion rate of substance P (125 pg (100 ml tissue)(-1) min(-1)) there was a greater (P < 0.05) increase in Q to the forearm (911 +/- 286%) than to the leg (243 +/- 58%). The responses to sodium nitroprusside (1 microg (100 ml tissue)(-1) min(-1)) were also greater (P < 0.05) in the forearm (925 +/- 164%) than in the leg (326 +/- 65%). These data indicate that vascular responses to both endothelium-dependent and -independent vasodilator agents are blunted in the leg compared to the forearm.

Acetylcholine↗
PubMed2004

Leg blood flow and VO2 during peak cycle exercise in younger and older women.

PURPOSE: To test the hypothesis that leg blood flow and leg O2 extraction during peak exercise are reduced with age in healthy normally active women. METHODS: Thirteen younger (20-27 yr) and 12 older (60-71 yr) nonendurance trained women performed graded upright leg cycling to maximum exertion (VO2peak), while leg blood flow (femoral vein thermodilution), cardiac output (acetylene rebreathing), mean arterial pressure (MAP, radial artery), and blood O2 contents were measured. RESULTS: Peak leg VO2 was 32% lower in the older versus younger women (0.81 +/- 0.06 vs 1.18 +/- 0.10 L x min(-1)) and was correlated with peak systemic VO2 (1.33 +/- 0.1 vs 1.78 +/- 0.1 L x min(-1)) in both groups. Peak leg blood flow and estimated leg vascular conductance were 29% and 38% lower, respectively, in the older women (both P < 0.001). Peak leg blood flow and peak estimated cardiac output were correlated in the older (r2 = 0.51, P = 0.02), but not younger (r2 = 0.10, P = 0.35), group. Estimates of peak systemic and leg arterial-venous O2 difference did not differ between groups (both P > 0.28). CONCLUSIONS: Reduced leg blood flow is a major contributor to the reduced peak systemic VO2 observed in older nonendurance trained women. Diminished leg blood flow during peak exercise in older women, in turn, is due to both central (reduced cardiac output) and peripheral (reduced leg vascular conductance) limitations.

Adult↗
PubMed2003

Age and aerobic exercise training effects on whole body and muscle protein metabolism.

Aging in humans is associated with loss of lean body mass, but the causes are incompletely defined. Lean tissue mass and function depend on continuous rebuilding of proteins. We tested the hypotheses that whole body and mixed muscle protein metabolism declines with age in men and women and that aerobic exercise training would partly reverse this decline. Seventy-eight healthy, previously untrained men and women aged 19-87 yr were studied before and after 4 mo of bicycle training (up to 45 min at 80% peak heart rate, 3-4 days/wk) or control (flexibility) activity. At the whole body level, protein breakdown (measured as [13C]leucine and [15N]phenylalanine flux), Leu oxidation, and protein synthesis (nonoxidative Leu disposal) declined with age at a rate of 4-5% per decade (P < 0.001). Fat-free mass was closely correlated with protein turnover and declined 3% per decade (P < 0.001), but even after covariate adjustment for fat-free mass, the decline in protein turnover with age remained significant. There were no differences between men and women after adjustment for fat-free mass. Mixed muscle protein synthesis also declined with age 3.5% per decade (P < 0.05). Exercise training improved aerobic capacity 9% overall (P < 0.01), and mixed muscle protein synthesis increased 22% (P < 0.05), with no effect of age on the training response for either variable. Fat-free mass, whole body protein turnover, and resting metabolic rate were unchanged by training. We conclude that rates of whole body and muscle protein metabolism decline with age in men and women, thus indicating that there is a progressive decline in the body's remodeling processes with aging. This study also demonstrates that aerobic exercise can enhance muscle protein synthesis irrespective of age.

Adult↗
PubMed2003

Impaired leg vasodilation during dynamic exercise in healthy older women.

The purpose of the present study was to test the hypothesis that leg blood flow responses during leg cycle ergometry are reduced with age in healthy non-estrogen-replaced women. Thirteen younger (20-27 yr) and thirteen older (61-71 yr) normotensive, non-endurance-trained women performed both graded and constant-load bouts of leg cycling at the same absolute exercise intensities. Leg blood flow (femoral vein thermodilution), mean arterial pressure (MAP; radial artery), mean femoral venous pressure, cardiac output (acetylene rebreathing), and blood O2 contents were measured. Leg blood flow responses at light workloads (20-40 W) were similar in younger and older women. However, at moderate workloads (50-60 W), leg blood flow responses were significantly attenuated in older women. MAP was 20-25 mmHg higher (P < 0.01) in the older women across all work intensities, and calculated leg vascular conductance (leg blood flow/estimated leg perfusion pressure) was lower (P < 0.05). Exercise-induced increases in leg arteriovenous O2 difference and O2 extraction were identical between groups (P > 0.6). Leg O2 uptake was tightly correlated with leg blood flow across all workloads in both subject groups (r2 = 0.80). These results suggest the ability of healthy older women to undergo limb vasodilation in response to submaximal exercise is impaired and that the legs are a potentially important contributor to the augmented systemic vascular resistance seen during dynamic exercise in older women.

Adult↗
PubMed2003

Augmented leg vasoconstriction in dynamically exercising older men during acute sympathetic stimulation.

Vasoconstrictor responsiveness to acute sympathetic stimulation declines with advancing age in resting skeletal muscle. The purpose of the present study was to determine if age-related reductions in sympathetic vasoconstrictor responsiveness also occur in exercising skeletal muscle. Thirteen younger (20-30 years) and seven older (62-74 years) healthy non-endurance-trained men performed cycle ergometer exercise at ~60 % of peak oxygen uptake while leg blood flow (femoral vein thermodilution), mean arterial blood pressure (radial artery catheter), and plasma adrenaline and noradrenaline concentrations were measured. After steady state was reached (i.e. ~4 min), acute sympathetic stimulation was achieved by immersing a hand in ice water for 2-4 min (cold pressor test, CPT). CPT tended to cause a larger increase in mean arterial blood pressure in older men (older (O): 16 +/- 3 mmHg; younger (Y): 10 +/- 2 mmHg) during exercise, but increases in arterial noradrenaline were similar (O: 2.56 +/- 0.96 nM; Y: 1.98 +/- 0.40 nM). However, the older men demonstrated a larger percentage reduction in exercising leg vascular conductance (leg blood flow/mean arterial pressure) during CPT compared to younger men (O: -13.6 +/- 3.1 %; Y: -1.5 +/- 4.3 %; P = 0.04). Leg blood flow tended to increase in the younger men, but not in the older men (P = 0.10). These results suggest, in contrast to what has been observed in resting skeletal muscle, that vasoconstrictor responsiveness to sympathetic stimulation is not reduced, but may be augmented in exercising muscle of healthy older humans. This could reflect a reduced ability of local substances (e.g. nitric oxide) to impair vasoconstriction in response to sympathetic stimulation during exercise in older humans.

Adult↗
PubMed2003

Leg blood flow during submaximal cycle ergometry is not reduced in healthy older normally active men.

The purpose of the present study was to test the hypothesis that leg blood flow responses during submaximal cycle ergometry are reduced with age in healthy normally active men. Eleven younger (20-25 yr) and eight older (62-73 yr) normotensive, nonendurance-trained men performed both graded and constant-load bouts of leg cycling at the same absolute and relative [% of peak O(2) consumption (Vo(2 peak))] exercise intensities while leg blood flow (femoral vein thermodilution), mean arterial pressure (MAP; radial artery), cardiac output (acetylene rebreathing), blood O(2) content, and plasma catecholamines were measured. Leg blood flow responses at the same absolute submaximal power outputs (20-100 W) and at a fixed systemic O(2) demand (1.1 l/min) did not differ between groups (P = 0.14-0.19), despite lower absolute levels of cardiac output in the older men (P < 0.05). MAP at the same absolute power outputs was 8-12 mmHg higher (P < 0.05) in the older men, but calculated leg vascular conductance responses (leg blood flow/MAP) were identical in the two groups (P > 0.9). At the same relative intensity (60% Vo(2 peak)), leg norepinephrine spillover rates were approximately twofold higher in the older men (P = 0.38). Exercise-induced increases in leg arterial-venous O(2) difference were identical between groups (P > 0.9) because both arterial and venous O(2) contents were lower in the older vs. younger men. These results suggest that the ability to augment active limb blood flow and O(2) extraction during submaximal large muscle mass exercise is not impaired but is well preserved with age in healthy men who are normally active.

Absorptiometry, Photon↗
PubMed2003

Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity.

Insulin resistance increases and muscle oxidative capacity decreases during aging, but lifestyle changes-especially physical activity-may reverse these trends. Here we report the effect of a 16-week aerobic exercise program (n = 65) or control activity (n = 37) performed by men and women aged 21-87 years on insulin sensitivity and muscle mitochondria. Insulin sensitivity, measured by intravenous glucose tolerance test, decreased with age (r = -0.32) and was related to abdominal fat content (r = -0.65). Exercise increased peak oxygen uptake (VO(2peak); 10%), activity of muscle mitochondrial enzymes (citrate synthase and cytochrome c oxidase, 45-76%) and mRNA levels of mitochondrial genes (COX4, ND4, both 66%) and genes involved in mitochondrial biogenesis (PGC-1alpha, 55%; NRF-1, 15%; TFAM, 85%). Exercise also increased muscle GLUT4 mRNA and protein (30-52%) and reduced abdominal fat (5%) and plasma triglycerides (25%). None of these changes were affected by age. In contrast, insulin sensitivity improved in younger people but not in middle-aged or older groups. Thus, the muscle mitochondrial response to 4 months of aerobic exercise training was similar in all age-groups, although the older people did not have an improvement in insulin sensitivity.

Adult↗