Reduced leg blood flow during dynamic exercise in older endurance-trained men

It is currentlyunclear whether aging alters the perfusion of active muscles duringlarge-muscle dynamic exercise in humans. To study this issue, directmeasurements of leg blood flow (femoral vein thermodilution) andsystemic arterial pressure during submaximal cycle ergometry (70, 140, and 210 W) were compared between six younger (Y; 22-30 yr) and sixolder (O; 55-68 yr) chronically endurance-trainedmen. Whole body O₂uptake, ventilation, and arterial and femoral venous samples forblood-gas, catecholamine, and lactate determinations were alsoobtained. Training duration (min/day), estimated leg muscle mass(dual-energy X-ray absorptiometry; Y, 21.5 ± 1.2 vs. O, 19.9 ± 0.9 kg), and blood hemoglobin concentration (Y, 14.9 ± 0.4 vs. O, 14.7 ± 0.2 g/dl) did not significantly differ (P > 0.05) between groups. Leg bloodflow, leg vascular conductance, and femoral venousO₂ saturation were ~20-30%lower in the older men at each work rate (allP < 0.05), despite similarlevels of whole body O₂ uptake. At210 W, leg norepinephrine spillover rates and femoral venous lactateconcentrations were more than twofold higher in the older men.Pulmonary ventilation was also higher in the older men at 140 (+24%)and 210 (+39%) W. These results indicate that leg blood flow andvascular conductance during cycle ergometer exercise are significantlylower in older endurance-trained men in comparison to their youngercounterparts. The mechanisms responsible for this phenomenon and theextent to which they operate in other groups of older subjects deservefurther attention.

     

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.     

Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men

Cardiovagal baroreflex sensitivity (BRS) declines with advancing age in healthy men. We tested the hypothesis that oxidative stress contributes mechanistically to this age-associated reduction. Eight young (23 +/- 1 yrs, means +/- SE) and seven older (63 +/- 3) healthy men were studied. Cardiovagal BRS was assessed using the modified Oxford technique (bolus infusion of 50-100 microg sodium nitroprusside, followed 60 s later by a 100- to 150-microg bolus of phenylephrine hydrochloride) in triplicate at baseline and during acute intravenous ascorbic acid infusion. At baseline, cardiovagal BRS (slope of the linear portion of the R-R interval-systolic blood pressure relation during pharmacological changes in arterial blood pressure) was 56% lower (P < 0.01) in older (8.3 +/- 1.6 ms/mmHg) compared with young (19.0 +/- 3.1 ms/mmHg) men. Ascorbic acid infusion increased plasma concentrations similarly in young (62 +/- 9 vs. 1,249 +/- 72 micromol/l for baseline and during ascorbic acid; P < 0.05) and older men (62 +/- 4 vs. 1,022 +/- 55 micromol/l; P < 0.05) without affecting baseline blood pressure, heart rate, carotid artery compliance, or the magnitude of change in systolic blood pressure in response to bolus sodium nitroprusside and phenylephrine hydrochloride infusion. Ascorbic acid (vitamin C) infusion increased cardiovagal BRS in older (Delta58 +/- 16%; P < 0.01), but not younger (Delta - 4 +/- 4%) men. These data provide experimental support for the concept that oxidative stress contributes mechanistically to age-associated reductions in cardiovagal BRS in healthy men.     

Effects of variations in intragastric volume on blood pressure and splanchnic blood flow during intraduodenal glucose infusion in healthy older subjects

The postprandial reduction in blood pressure (BP) is triggered by the interaction of nutrients with the small intestine and associated with an increase in splanchnic blood flow. Gastric distension may attenuate the postprandial fall in BP. The aim of this study was to determine the effects of differences in intragastric volume, including distension at a low (100 ml) volume, on BP and superior mesenteric artery (SMA) blood flow responses to intraduodenal glucose in healthy older subjects. BP and heart rate (HR; automated device), SMA blood flow (Doppler ultrasound), mesenteric vascular resistance (MVR), and plasma norepinephrine of nine male subjects (65-75 yr old) were measured after an overnight fast on 4 separate days in random order. On each day, subjects were intubated with a nasoduodenal catheter, incorporating a duodenal infusion port, and orally with a second catheter, incorporating a barostat bag, positioned in the fundus. Each subject received a 60-min (t = 0-60 min) intraduodenal glucose infusion (3 kcal/min) and gastric distension at a volume of 1) 0 ml (V0), 2) 100 ml (V100), 3) 300 ml (V300), or 4) 500 ml (V500). Systolic BP fell (P < 0.05) during V0, but not during V100, V300, or V500. In contrast, HR (P < 0.01) and SMA blood flow (P < 0.001) increased and MVR decreased (P < 0.05) comparably on all 4 days. Plasma norepinephrine rose (P < 0.01) in response to intraduodenal glucose, with no difference between the four treatments. There was a relationship between the areas under the curve for the change in systolic BP from baseline with intragastric volume (r = 0.60, P < 0.001). In conclusion, low-volume (≤100 ml) gastric distension has the capacity to abolish the fall in BP induced by intraduodenal glucose in healthy older subjects without affecting SMA blood flow or MVR. These observations support the concept that nonnutrient gastric distension prior to a meal has potential therapeutic applications in the management of postprandial hypotension.     

Lack of age-related decreases in basal whole leg blood flow in resistance-trained men.

Reductions in basal leg blood flow have been implicated in the pathogenesis of metabolic syndrome and functional impairment in humans. We tested the hypothesis that reductions in basal whole leg blood flow with age are either absent or attenuated in those who perform regular strength training. A total of 104 normotensive men aged 20-34 yr (young) and 35-65 yr (middle aged), who were either sedentary or resistance trained, were studied. Mean and diastolic blood pressures were higher (P < 0.05-0.001) in the middle-aged compared with the young men, but there were no significant differences between the sedentary and resistance-trained groups. In the sedentary group, basal whole leg blood flow (duplex Doppler ultrasound) and vascular conductance were lower ( approximately 30 and approximately 38%, respectively; P < 0.01) in the middle-aged compared with the young men. There were no such age-related differences in the resistance-trained group. In the young men, basal whole leg blood flow and vascular conductance were not different between the two activity groups, but, in the middle-aged men, they were higher ( approximately 35 and approximately 36%, respectively; P < 0.01) in the resistance-trained men than in the sedentary men. When blood flow and vascular conductance were expressed relative to the leg muscle mass, the results were essentially the same. We concluded that the age-related reduction in basal whole leg blood flow is absent in resistance-trained men. These results suggest that resistance training may favorably influence leg perfusion in aging humans, independent of its impact on leg muscle mass.     

Cardiorespiratory and subjective responses to prolonged arm and leg exercise in healthy young and older men

Ten young (aged 23–30 years) and nine older (aged 54–59 years) healthy men with a similar size of limb muscle mass performed arm crank and leg cycle exercise for 30 min at relative exercise intensities of 50% and 75% of maximal oxygen uptake for the corresponding muscle group. In the tests, heart rate, blood pressure, gas exchange variables, rating of perceived exertion and blood lactate concentration were measured. The limb muscle mass was determined by anthropometric measurements. At the 75% target exercise level, four of the older men and two of the young men could not complete the arm-cranking test, and one of the older men and two of the young men could not complete the leg-cycle test. During arm-cranking the absolute exercise intensity was similar for the young and older men because of similar maximal values during arm-cranking. But during leg-cycling the absolute excercise intensity was higher for the young men than for the older men due to the difference in corresponding maximal values. During arm-cranking there were no significant differences in the physiological responses between the age groups except that a higher ventilatory response was noted among the older compared to the young men. During leg-cycling the heart rate values were higher among the young compared to the older men. But, when the heart rate values were expressed as a percentage of maximal heart rate in the corresponding maximal tests, no significant differences between the age groups were found. The results indicated that 30-min of arm or leg exercise at the same relative submaximal excercise intensity produces a similar degree of physiological strain in healthy older compared to young men. During arm-cranking, the young and the older men exercised at the same external intensity, indicating a similar ability to perform prolonged excercise using smaller muscle groups expressed both in absolute and relative terms. Accepted: 7 October 1996     

Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women.

Basal whole leg blood flow and vascular conductance are reduced in estrogen-deficient postmenopausal compared with premenopausal women. The underlying mechanisms are unknown, but oxidative stress could be involved. We studied 9 premenopausal [23 +/- 1 yr (mean +/- SE)] and 20 estrogen-deficient postmenopausal (55 +/- 1 yr) healthy women. During baseline control, oxidized low-density lipoprotein (LDL), a marker of oxidative stress, was 50% greater in the postmenopausal women (P < 0.001). Basal whole leg blood flow (duplex ultrasound of femoral artery) was 34% lower in the postmenopausal women because of a 38% lower leg vascular conductance (P < 0.0001); mean arterial pressure was not different. Intravenous administration of a supraphysiological dose of the antioxidant ascorbic acid increased leg blood flow by 15% in the postmenopausal women as a result of an increase in leg vascular conductance (both P < 0.001), but it did not affect leg blood flow in premenopausal controls or mean arterial pressure in either group. In the pooled subjects, the changes in leg blood flow and leg vascular conductance with ascorbic acid were related to baseline plasma oxidized LDL (r = 0.46 and 0.53, P < 0.01) and waist-to-hip ratio and total body fat (r = 0.41-0.44, all P < 0.05). Our results are consistent with the hypothesis that oxidative stress contributes to chronic leg vasoconstriction and reduced basal whole leg blood flow in estrogen-deficient postmenopausal women. This oxidative stress-related suppression of leg vascular conductance and blood flow may be linked in part to increased total and abdominal adiposity.     

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.     

Elevation in resting blood flow attenuates exercise hyperemia.

These experiments tested the hypothesis that elevating muscle blood flow before exercise would wash out vasoactive substances produced by muscle contraction and reduce the magnitude of exercise hyperemia and/or delay the response. In chronically instrumented dogs (n = 7), hindlimb blood flow was measured with chronically implanted flow probes during mild treadmill exercise. In an anesthetized preparation (n = 8), arterial and venous blood flows of a single hindlimb were obtained during 1-s tetanic contractions evoked by electrical stimulation of the cut sciatic nerve. Elevation of blood flow by intra-arterial infusion of adenosine attenuated the increase in flow during exercise and tetanic contraction by 48 and 47%, respectively. No delay was observed in the latency to peak flow. The attenuated hyperemic response to exercise or contraction is best explained by washout of vasoactive substance(s) produced by contracting muscle, but the residual response suggests that a metabolic mediator may not be the sole explanation for exercise hyperemia.     

Enhanced endothelin-1-mediated leg vascular tone in healthy older subjects.

Advanced age is associated with a decreased leg blood flow and reduced physical activity. Endothelin (ET-1), a powerful vasoconstrictor, may play a role in the increased leg vascular tone in older men. objectives: to assess the ET-1-mediated vascular tone in the legs of healthy sedentary older men, both before and after 8 wk of exercise training. methods: in 8 younger subjects (19-50 yr) and 8 older men (67-76 yr), bilateral leg blood flow was measured using venous occlusion plethysmography before and after antagonizing ET-1 (using selective ET(A/B)-receptor antagonists). In older men, reversibility of the observations was assessed after 8 wk of cycling. results: ET-receptor inhibition increased leg blood flow significantly more in older men compared with younger individuals (29 +/- 9% and 10 +/- 4%, respectively, P < 0.05). Eight-week cycling training increased baseline blood flow in older men. The blood flow response to ET-receptor inhibition in older men was not affected by the training program (25 +/- 8%, P > 0.05 for comparison with pretraining). The flow ratio (blood flows infused leg/noninfused leg) decreased significantly by training from 26 +/- 8% to 7+3% (P < 0.05). CONCLUSION: the increased baseline vascular tone in aging is at least in part mediated by the endothelin. Eight-weeks cycling training in older sedentary men decreased leg vascular tone and seems to partly decrease the ET-1-mediated vascular tone.     

Effect of restricted blood flow on exercise-induced hormone changes in healthy men

To test the influence of the accumulation of metabolites on exercise-induced hormone responses, plasma concentrations of cortisol, growth hormone (GH), insulin, testosterone, thyrotropin (TSH), free thyroxine (fT₄) and triiodothyronine (T₃) were compared during exercise performed under normal conditions (control) and under conditions of restricted blood flow of exercising leg muscles (ischaemia) in nine healthy young men. Blood supply was reduced by 15%–20% by the application of 50 mmHg external pressure over the exercising leg. During 45-min cycling exercise during ischaemia the increase in GH concentration was twice as large as under normal conditions. Despite the below-threshold exercise intensity for activation of the pituitary-adrenocortical system under normal exercise conditions ischaemic exercise elicited cortisol and T₃ responses (concentration increases of 83% and 9.5%, respectively). Ischaemic exercise attenuated the decrease of plasma insulin concentration found under normal conditions. The concentrations of testosterone, TSH and fT₄ were not changed significantly during exercise performed in either condition. The results support the suggested essential role of muscle metaboreceptors in the control of hormone responses during muscle activity. Accepted: 6 November 1997     

Sex steroid hormones and cognitive functioning in healthy, older men

The precise impact of age-related changes in hormone levels on cognition in men is still unclear due to differing study designs and contradictory findings. This study was undertaken to examine the relationship between endogenous sex hormone levels and cognitive functioning in healthy older men using a comprehensive battery of neuropsychological tests and measurement of serum sex hormone levels. Verbal learning and memory, visual-motor processing, spatial abilities, working memory and attention, and levels of testosterone and estradiol were evaluated in 54 healthy older men. Regression analyses revealed significant curvilinear associations between working memory function and both free and bioavailable testosterone levels, suggesting that an optimal hormone level may exist for maximal performance on tasks of executive/frontal lobe functioning. However, no other relationships were evident between either estradiol or testosterone levels and any of the other cognitive functions evaluated. Hormone assays performed at the end of the study revealed that a considerable portion of the healthy elderly men in our sample met criteria for hypogonadism and suggests that their low hormone levels may have mitigated against discovering other significant hormone-cognition relationships.