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Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation with sodium nitrite, a precursor of NO, ameliorates age-related vascular endothelial dysfunction and arterial stiffness in mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose of this study was to determine the safety, feasibility, and efficacy of oral sodium nitrite supplementation for improving vascular function in middle-aged and older adults and to identify related circulating metabolites. Ten weeks of sodium nitrite (80 or 160 mg/day, capsules, TheraVasc; randomized, placebo control, double blind) increased plasma nitrite acutely (5- to 15-fold, P < 0.001 vs. placebo) and chronically ( P < 0.10) and was well tolerated without symptomatic hypotension or clinically relevant elevations in blood methemoglobin. Endothelial function, measured by brachial artery flow-mediated dilation, increased 45-60% vs. baseline ( P < 0.10) without changes in body mass or blood lipids. Measures of carotid artery elasticity (ultrasound and applanation tonometry) improved (decreased β-stiffness index, increased cross-sectional compliance, P < 0.05) without changes in brachial or carotid artery blood pressure. Aortic pulse wave velocity was unchanged. Nitrite-induced changes in vascular measures were significantly related to 11 plasma metabolites identified by untargeted analysis. Baseline abundance of multiple metabolites, including glycerophospholipids and fatty acyls, predicted vascular changes with nitrite. This study provides evidence that sodium nitrite supplementation is well tolerated, increases plasma nitrite concentrations, improves endothelial function, and lessens carotid artery stiffening in middle-aged and older adults, perhaps by altering multiple metabolic pathways, thereby warranting a larger clinical trial.

Increasing age is associated with declines in multiple domains of physiological function leading to an increased risk of morbidity, disability, and mortality in older adults. Central to these declines in physiological function is a reduction in the bioavailability of the ubiquitous signaling molecule nitric oxide (NO). Supplementation with precursors of NO, nitrate, and nitrite, improves select vascular, physical, and cognitive functions in middle-aged and older adults and may improve age-associated inflammation and oxidative stress. Collectively, current evidence suggests that nitrate and nitrite supplementation represent promising therapeutic strategies for enhancing physiological function with aging and reducing the risk of age-associated disability and risk of chronic diseases.

In the present study, we tested the hypothesis that age-associated vascular endothelial dysfunction is exacerbated by IFG (impaired fasting plasma glucose) and that regular aerobic exercise prevents this effect. Data were analysed from a cohort of 131 non-smoking men and women without overt clinical disease. Compared with young adult controls (age=24±1 years, n=29; values are means±S.E.M.), brachial artery FMD (flow-mediated dilation), a measure of conduit artery EDD (endothelium-dependent dilation), was 33% lower [7.93±0.33 against 5.27±0.37%Δ (% change), P45 min/day for ≥5 days/week, 62±1 years, n=23) compared with their non-exercising peers and only slightly less than young controls (P

The demographics of ageing are changing dramatically such that there will be many more older adults in the near future. This setting is projected to produce a new 'boomer-driven' epidemic of physiological dysfunction, disability and risk of chronic degenerative disorders, including cardiovascular diseases. Standing out against this dreary biomedical forecast are Masters athletes, a group of middle-aged and older adults who engage in regular vigorous physical training and competitive sport. Compared with their sedentary/less active (untrained) peers, Masters athletes who perform endurance training-based activities demonstrate a more favourable arterial function-structure phenotype, including lower large elastic artery stiffness, enhanced vascular endothelial function and less arterial wall hypertrophy. As such, they may represent an exemplary model of healthy or 'successful' vascular ageing. In contrast, Masters athletes engaged primarily/exclusively in intensive resistance training exhibit less favourable arterial function-structure than their endurance-trained peers and, in some instances, untrained adults. These different arterial properties are probably explained in large part by the different intravascular mechanical forces generated during endurance versus resistance exercise-related training activities. The more favourable arterial function-structure profile of Masters endurance athletes may contribute to their low risk of clinical cardiovascular diseases.

Monitoring alterations in fingertip temperature during ischaemia and the subsequent hyperaemia provides a novel way of studying microvascular reactivity. The relations between parameters characterizing blood perfusion and the thermal response of fingertips were studied using experimental and theoretical approaches. During the experimental protocol, two brachial artery occlusion tests were conducted in 12 healthy volunteers, and fingertip temperature, heat flux and skin perfusion using laser Doppler flowmetry (LDF) were measured. The temperature curves provide a smooth and robust response that is able to capture occlusion and reperfusion. The temperature fall during occlusion as well as the maximum temperature recorded depended linearly on the initial temperature. The magnitude of the LDF signal was associated with local tissue temperature and followed an exponential response. Heat flux measurements demonstrated rapid changes and followed variations in blood perfusion closely. The time points at which the heat flux reached its maximum corresponded to the time at which the fingertip temperature curves showed an inflection point after cuff release. The time required for the fingertip temperature to arrive at the maximum temperature was greater than the time to peak for the heat flux signal, which was greater than the LDF signal to reach a maximum. The time lag between these signals was a function of the finger size and finger temperature at the moment reperfusion restarted. Our present results indicate that finger temperature, heat flux and perfusion display varying rates of recovery following ischaemic stimuli and that differential responses are associated with the initial finger temperature.

Contrary to aerobic exercise, strength training (ST) is associated with decreased central arterial compliance in young men. It is unknown whether ST, with or without concurrent endurance training, would have a similar effect in older adults with reduced baseline arterial compliance.The primary aim of this study was to determine the effect of a ST program on central arterial compliance in middle-aged and older adults.Randomized, controlled intervention study in which 37 healthy, sedentary men and women (52+/-2 years) performed 13 weeks of ST (n=13), ST+aerobic exercise (n=12) or stretching exercises as a control group (n=12).Participants were rigorously screened for cardiovascular disease and underwent pre-post testing for carotid arterial compliance (via simultaneous ultrasound and applanation tonometry), carotid-femoral pulse wave velocity, plasma endothelin-1 and angiotensin II concentrations and carotid artery vasoreactivity (cold pressor test).ST performed alone, or in conjunction with aerobic exercise, improved maximal muscle strength and increased total lean body mass (both P0.01). No significant changes were observed in carotid artery compliance or carotid-femoral pulse wave velocity following ST or ST+aerobic exercise. Carotid artery compliance increased significantly (23%) following stretching which may be attributed to a reduction in carotid pulse pressure. No significant changes were observed in plasma vasoconstrictor hormones or carotid artery vasoreactivity following the interventions.Thirteen weeks of moderate ST two or three times per week does not reduce central arterial compliance in middle-aged and older adults.

Advancing age is associated with reductions in nitric oxide bioavailability and changes in metabolic activity, which are implicated in declines in motor and cognitive function. In preclinical models, sodium nitrite supplementation (SN) increases plasma nitrite and improves motor function, whereas other nitric oxide-boosting agents improve cognitive function. This pilot study was designed to translate these findings to middle-aged and older (MA/O) humans to provide proof-of-concept support for larger trials. SN (10 weeks, 80 to 160 mg/day capsules, TheraVasc, Inc.) acutely and chronically increased plasma nitrite and improved performance on measures of motor and cognitive outcomes (all p

Despite the increased popularity of heart rate (HR) monitors, endurance-trained adults as well as habitual exercisers often use pulse rate palpation to periodically monitor exercise intensity. However, due to the rapid recovery of HR following exercise bouts, post-exercise palpation of pulse rates may underestimate exercise HR. To test this hypothesis, we studied 20 young physically active adults performing two sets of exercise for 5 min at 70% and 85% of maximal HR on the treadmill; one with carotid and another with radial pulse count. Post-exercise palpation of pulse rate was lower (P < 0.01) than the actual HR during exercise, underestimating exercise HR by 20-27 bpm (beats per min). Even when ECG tracings of HR were analyzed immediately after exercise (0-15 s), a significant underestimation of exercise HR (7-9 bpm) still persisted (P < 0.05). Following exercise, pulse rate obtained by carotid palpation at both intensities and radial palpation at the lower intensity was no different from the corresponding HR measured with ECG. In the radial artery trial at the higher exercise intensity, pulse rate following exercise was lower (10 bpm; P < 0.05) than ECG-derived HR. Arterial stiffness, which is closely associated with arterial baroreflex sensitivity, was not significantly related to the changes in HR with carotid palpation. We concluded that post-exercise pulse palpations may not be appropriate as an indicator of exercise intensity in habitual exercisers.

Decreased central arterial compliance is an emerging risk factor for cardiovascular disease. Resistance training is associated with reductions in the elastic properties of central arteries. Currently, it is not known whether this reduction is from one bout of resistance exercise or from an adaptation to multiple bouts of resistance training. Sixteen healthy sedentary or recreationally active adults (11 men and 5 women, age 27 ± 1 yr) were studied under parallel experimental conditions on 2 separate days. The order of experiments was randomized between resistance exercise (9 resistance exercises at 75% of 1 repetition maximum) and sham control (seated rest in the exercise room). Baseline hemodynamic values were not different between the two experimental conditions. Carotid arterial compliance (via simultaneous B-mode ultrasound and applanation tonometry) decreased and β-stiffness index increased ( P < 0.01) immediately and 30 min after resistance exercise. Immediately after resistance exercise, carotid systolic blood pressure increased ( P < 0.01), although no changes were observed in brachial systolic blood pressure at any time points. These measures returned to baseline values within 60 min after the completion of resistance exercise. No significant changes in these variables were observed during the sham control condition. These results indicate that one bout of resistance exercise acutely decreases central arterial compliance, but this effect is sustained for

Brachial-ankle pulse wave velocity (baPWV) is a promising technique to assess arterial stiffness conveniently. However, it is not known whether baPWV is associated with well-established indices of central arterial stiffness. We determined the relation of baPWV with aortic (carotid-femoral) PWV, leg (femoral-ankle) PWV, and carotid augmentation index (AI) by using both cross-sectional and interventional approaches. First, we studied 409 healthy adults aged 18-76 years. baPWV correlated significantly with aortic PWV (r = 0.76), leg PWV (r = 0.76), and carotid AI (r = 0.52). A stepwise regression analysis revealed that aortic PWV was the primary independent correlate of baPWV, explaining 58% of the total variance in baPWV. Additional 23% of the variance was explained by leg PWV. Second, 13 sedentary healthy men were studied before and after a 16-week moderate aerobic exercise intervention (brisk walking to jogging; 30-45 min/day; 4-5 days/week). Reductions in aortic PWV observed with the exercise intervention were significantly and positively associated with the corresponding changes in baPWV (r = 0.74). A stepwise regression analysis revealed that changes in aortic PWV were the only independent correlate of changes in baPWV (beta = 0.74), explaining 55% of the total variance. These results suggest that baPWV may provide qualitatively similar information to those derived from central arterial stiffness although some portions of baPWV may be determined by peripheral arterial stiffness.

Resistance exercise involves muscular contractions that can render downstream tissues ischemic and may precondition the vasculature against ischemia–reperfusion (IR) injury, but it is unknown if habitual resistance exercise protects against IR injury in humans. We determined the magnitude and recovery from endothelial IR injury induced by forearm occlusion in 22 healthy young sedentary and resistance-trained adults. After IR injury, brachial artery flow-mediated dilation (FMD) significantly decreased by 36% in sedentary, but not resistance-trained subjects and fully recovered within 45min. Though HDL-cholesterol, handgrip strength and systolic blood pressure were significantly associated with FMD 15min after IR injury, the change in FMD from before to 15min after IR injury was not associated with any subject characteristics. These results are consistent with the notion that habitual resistance exercise may protect against endothelial IR injury in young adults, presumably through effects analogous to ischemic preconditioning.

Vascular endothelial dysfunction develops with aging as a result of insufficient nitric oxide (NO) bioavailability. Supplementation with nitrite, a precursor to NO, may improve NO bioavailability. We tested the safety, dose (80 vs. 160 mg/d), duration (4 and 10 weeks), and efficacy of oral sodium nitrite for improving endothelial dysfunction in middle-aged and older (MA/O) adults (n=28, 61±1 yr) in a randomized, placebo-controlled, double-blind pilot intervention study. Both doses of nitrite acutely increased plasma nitrite (10 to 20-fold, p

Declines in exercise capacity with aging are associated with increased risk of disability and mortality. Dietary interventions that increase circulating nitrite may improve exercise capacity. We pe...

Reduced nitric oxide (NO) bioavailability contributes to physiological dysfunction with aging. Oral sodium nitrite supplementation (SN) increases circulating nitrite, a precursor of NO, and improve...

Aging is the major risk factor for cardiovascular diseases (CVD). This is attributable primarily to adverse changes in arteries, notably, increases in large elastic artery stiffness and endothelial dysfunction mediated by inadequate concentrations of the vascular-protective molecule, nitric oxide (NO), and higher levels of oxidative stress and inflammation. Inorganic nitrite is a promising precursor molecule for augmenting circulating and tissue NO bioavailability because it requires only a one-step reduction to NO. Nitrite also acts as an independent signaling molecule, exerting many of the effects previously attributed to NO. Results of recent studies indicate that nitrite may be effective in the treatment of vascular aging. In old mice, short-term oral sodium nitrite supplementation reduces aortic pulse wave velocity, the gold-standard measure of large elastic artery stiffness, and ameliorates endothelial dysfunction, as indicated by normalization of NO-mediated endothelium-dependent dilation. These improvements in age-related vascular dysfunction with nitrite are mediated by reductions in oxidative stress and inflammation, and may be linked to increases in mitochondrial biogenesis and health. Increasing nitrite levels via dietary intake of nitrate appears to have similarly beneficial effects in many of the same physiological and clinical settings. Several clinical trials are being performed to determine the broad therapeutic potential of increasing nitrite bioavailability on human health and disease, including studies related to vascular aging. In summary, inorganic nitrite, as well as dietary nitrate supplementation, represents a promising therapy for treatment of arterial aging and prevention of age-associated CVD in humans.

Flow-mediated dilation (FMD) is a non-invasive index of endothelial function. In an attempt to standardize FMD for shear stimulus, shear rate (velocity/diameter), rather than shear stress (viscosity*velocity/diameter), is commonly used as a surrogate measure, although it is limited by individual differences in blood viscosity. The purpose of this study was to determine the contribution of whole blood viscosity to FMD and other key measures of vascular function. Blood viscosity, FMD, carotid artery compliance, and carotid–femoral pulse wave velocity (cfPWV) were measured in 98 apparently healthy adults varying widely in age (18–63 years). Whole blood viscosity was not significantly correlated with FMD, cfPWV, or carotid artery compliance. Shear rate was a stronger correlate with FMD than shear stress that takes blood viscosity into account ( r = 0.43 vs 0.28). No significant differences were observed between whole blood viscosity and traditional risk factors for cardiovascular disease. Age was positively correlated with cfPWV ( r = 0.65, p < 0.001) and negatively correlated with FMD ( r = −0.24, p < 0.05) and carotid artery compliance ( r = −0.45, p < 0.01). Controlling for viscosity did not reduce the strength of these relations. These results indicate that whole blood viscosity does not significantly impact measures of vascular function and suggests that the common practice to use shear rate, rather than shear stress, in the adjustment of FMD is valid.

We performed a pilot study to test the hypothesis that acute oral ingestion of tetrahydrobiopterin (BH(4)), a key cofactor modulating vascular nitric oxide (NO) synthase activity, improves large elastic artery stiffness with aging in men.Healthy older (63 ± 2 years; n = 8) and young (age 25 ± 1 years; n = 6) men were studied 3 h after ingestion of BH(4) (10 mg·kg(-1) body weight) or placebo on separate days in a randomized, placebo-controlled, double-blind study.Baseline carotid artery compliance was 37% lower (0.17 ± 0.02 vs. 0.22 ± 0.02 mm/mm Hg·10(-1)) and β-stiffness was 42% higher (7.3 ± 1.1 vs. 4.2 ± 0.5 AU) in the older men (both P0.05). BH(4) ingestion markedly increased circulating BH(4) concentrations in both groups (17-19-fold, P0.05), but increased compliance (+39% to 0.23 ± 0.02 mm/mm Hg·10(-1), P0.01) and decreased β-stiffness index (-27% to 5.3 ± 0.7 AU, P0.01) only in the older men. BH(4) also reduced carotid systolic blood pressure (SBP) in the older men (P0.05).These preliminary results support the possibility that limited BH(4) bioavailability contributes to impaired carotid artery compliance in healthy older men. Further studies are needed to determine if increasing BH(4) bioavailability though oral BH(4) supplementation may have therapeutic efficacy for improving large elastic artery compliance and reducing central SBP with aging.

One of the most commonly evaluated features of the arterial pressure waveforms is augmentation index (AI). Multiple devices have been developed and marketed that measure AI at peripheral arteries. Currently, it is not known if and how these measures of AI are related. Aortic and radial AI (using SphygmoCor), rad ial AI (Omron), and fi nger AI (Itamar) were measured in 40 apparently healthy subjects. All the AI values were correlated with each other with Pearson r-values ranging from 0.78 to 0.94. The coefficients of variation ranged from 3.4 to 20.0%. We concluded that even though the absolute values derived by each technique were different, there were high and significant correlations between AI values.

Monitoring alterations in fingertip temperature during ischaemia and the subsequent hyperaemia provides a novel way of studying microvascular reactivity. The relations between parameters characterizing blood perfusion and the thermal response of fingertips were studied using experimental and theoretical approaches. During the experimental protocol, two brachial artery occlusion tests were conducted in 12 healthy volunteers, and fingertip temperature, heat flux and skin perfusion using laser Doppler flowmetry (LDF) were measured. The temperature curves provide a smooth and robust response that is able to capture occlusion and reperfusion. The temperature fall during occlusion as well as the maximum temperature recorded depended linearly on the initial temperature. The magnitude of the LDF signal was associated with local tissue temperature and followed an exponential response. Heat flux measurements demonstrated rapid changes and followed variations in blood perfusion closely. The time points at which the heat flux reached its maximum corresponded to the time at which the fingertip temperature curves showed an inflection point after cuff release. The time required for the fingertip temperature to arrive at the maximum temperature was greater than the time to peak for the heat flux signal, which was greater than the LDF signal to reach a maximum. The time lag between these signals was a function of the finger size and finger temperature at the moment reperfusion restarted. Our present results indicate that finger temperature, heat flux and perfusion display varying rates of recovery following ischaemic stimuli and that differential responses are associated with the initial finger temperature.

The clinical importance of vascular reactivity as an early marker of atherosclerosis has been well established, and a number of established and emerging techniques have been employed to provide measurements of peripheral vascular reactivity. However, relations between these methodologies are unclear as each technique evaluates different physiological aspects related to micro- and macrovascular reactive hyperemia. To address this question, a total of 40 apparently healthy normotensive adults, 19–68 yr old, underwent 5 min of forearm suprasystolic cuff-induced ischemia followed by postischemic measurements. Measurements of vascular reactivity included 1) flow-mediated dilatation (FMD), 2) changes in pulse wave velocity between the brachial and radial artery (ΔPWV), 3) hyperemic shear stress, 4) reactive hyperemic flow, 5) reactive hyperemia index (RHI) assessed by fingertip arterial tonometry, 6) fingertip temperature rebound (TR), and 7) skin reactive hyperemia. FMD was significantly and positively associated with RHI ( r = 0.47) and TR ( r = 0.45) (both P < 0.01) but not with reactive hyperemic flow or hyperemic shear stress. There was no correlation between two measures of macrovascular reactivity (FMD and ΔPWV). Skin reactive hyperemia was significantly associated with RHI ( r = 0.55) and reactive hyperemic flow ( r = 0.35) (both P < 0.05). There was a significant association between reactive hyperemia and RHI ( r = 0.30; P < 0.05). In more than 75% of cases, vascular reactivity measures were not significantly associated. We concluded that associations among different measures of peripheral micro- and macrovascular reactivity were modest at best. These results suggest that different physiological mechanisms may be involved in changing different measures of vascular reactivity.

An innovative exercise machine, which mimics the movement of horseback riding, has been made available in the market. As an initial step in characterizing this device, we determined the cardiovascular and metabolic responses to exercise. Twenty apparently healthy subjects rode the device (Equus) on day 1. The upper body exercises were added on day 2, to see whether cardiac and metabolic demands were further elevated (Equus+aerobics). After 10 min of continuous exercise, oxygen consumption increased significantly. In the Equus+aerobics condition, increase in oxygen consumption was significant as early as 4 min into the graded exercise test. Overall oxygen consumption was greater in the Equus+aerobics condition than in the Equus condition (P

Age-related reductions in basal limb blood flow and vascular conductance are associated with the metabolic syndrome, functional impairments, and osteoporosis. We tested the hypothesis that a strength training program would increase basal femoral blood flow in aging adults. Twenty-six sedentary but healthy middle-aged and older subjects were randomly assigned to either a whole body strength training intervention group (52 ± 2 yr, 3 men, 10 women) who underwent three supervised resistance training sessions per week for 13 wk or a control group (53 ± 2 yr, 4 men, 9 women) who participated in a supervised stretching program. At baseline, there were no significant differences in blood pressure, cardiac output, basal femoral blood flow (via Doppler ultrasound), vascular conductance, and vascular resistance between the two groups. The strength training group increased maximal strength in all the major muscle groups tested ( P < 0.05). Whole body lean body mass increased ( P < 0.05) with strength training, but leg fat-free mass did not. Basal femoral blood flow and vascular conductance increased by 55–60% after strength training (both P < 0.05). No such changes were observed in the control group. In both groups, there were no significant changes in brachial blood pressure, plasma endothelin-1 and angiotensin II concentrations, femoral artery wall thickness, cardiac output, and systemic vascular resistance. Our results indicate that short-term strength training increases basal femoral blood flow and vascular conductance in healthy middle-aged and older adults.

Acute and chronic smoking reduces peripheral blood flow and shear stress, contributing to the increased incidence of peripheral arterial disease in smokers. Currently, it is not known whether physical activity status influences peripheral blood flow among chronic smokers. Blood flow was measured using Doppler ultrasound on the common femoral artery in nine young otherwise healthy sedentary smokers (eight males/one female) and nine physically-active smokers (six males/three females). Physically-active smokers performed strenuous exercise 4.4 times/week for 8 h/week. No significant differences in body fat, blood pressure, and total cholesterol were observed between groups. Basal femoral artery blood flow was approximately 50% higher in physically-active smokers compared with sedentary smokers (259+/-108 ml min(-1) versus 173+/-47 ml min(-1), P

Cross-sectional studies reported that chronic resistance training is associated with arterial stiffening in men. These findings are in marked contrast to those found with aerobic exercise and may have important clinical relevance with regard to cardiovascular disease risk. However, the effect of resistance training on arterial stiffness has not been confirmed by interventional studies nor has this relation been investigated in women.To determine whether a strength training program increases regional and central arterial stiffness in women, 23 healthy young women (29+/-1 years; mean+/-SD) participated in a high-intensity strength and power training program for 11 weeks. Ten other women (27+/-2 years) served as time controls.In the intervention group, one repetition maximal strength increased 12% to 17% (P.0001), and leg fat-free mass (via DEXA) increased significantly. Brachial blood pressure (BP) and fasting plasma lipid and lipoprotein concentrations did not change across the 11 weeks. Carotid augmentation index, a measure of arterial wave reflection and arterial stiffness, increased from -8%+/-13% to 1%+/-18% (P.05), and carotid-femoral pulse wave velocity increased (791+/-88 v 833+/-96 cm/sec; P.05). There were no changes in femoral-ankle pulse wave velocity, a segmental measure of peripheral arterial stiffness.We concluded that a high-intensity resistance training program increases arterial stiffness and wave reflection in young healthy women. Our present interventional results are consistent with the previous cross-sectional studies in men in which high-intensity strength training is associated with arterial stiffening.

We recently published an original research article in Clinical Science reporting that the age-associated impairment in brachial artery FMD (flow-mediated dilation), a non-invasive measure of conduit artery endothelial function, was exacerbated in MA/O (middle-aged and older) adults with IFG (impaired fasting plasma glucose) concentrations, but this was not observed in MA/O adults with IFG who perform regular aerobic exercise [1]. This paper was the latest report in an extensive series of studies performed by our laboratory over the last decade investigating the effects of aging on vascular endothelial function in humans, the modulatory influences involved and the underlying mechanisms [2]. Several of the articles in this series have reported results on brachial artery FMD among different groups of young and MA/O healthy adults, as was the case in the present study [1]. After the publication of our paper [1], Professor Atkinson in his Correspondence to the Journal has suggested that a statistical issue … We recently published an original research article in Clinical Science reporting that the age-associated impairment in brachial artery FMD (flow-mediated dilation), a non-invasive measure of conduit artery endothelial function, was exacerbated in MA/O (middle-aged and older) adults with IFG (impaired fasting plasma glucose) concentrations, but this was not observed in MA/O adults with IFG who perform regular aerobic exercise [1]. This paper was the latest report in an extensive series of studies performed by our laboratory over the last decade investigating the effects of aging on vascular endothelial function in humans, the modulatory influences involved and the underlying mechanisms [2]. Several of the articles in this series have reported results on brachial artery FMD among different groups of young and MA/O healthy adults, as was the case in the present study [1]. After the publication of our paper [1], Professor Atkinson in his Correspondence to the Journal has suggested that a statistical issue …

Regular endurance exercise increases central arterial compliance, whereas resistance training decreases it. It is not known how the vasculature adapts to a combination of endurance and resistance training. Rowing is unique, because its training encompasses endurance- and strength-training components. We used a cross-sectional study design to determine arterial compliance of 15 healthy, habitual rowers [50 ± 9 (SD) yr, 11 men and 4 women] and 15 sedentary controls (52 ± 8 yr, 10 men and 5 women). Rowers had been training 5.4 ± 1.2 days/wk for 5.7 ± 4.0 yr. The two groups were matched for age, body composition, blood pressure, and metabolic risk factors. Central arterial compliance (simultaneous ultrasound and applanation tonometry on the common carotid artery) was higher ( P < 0.001) and carotid β-stiffness index was lower ( P < 0.001) in rowers than in sedentary controls. There were no group differences for measures of peripheral (femoral) arterial stiffness. The higher central arterial compliance in rowers was associated with a greater cardiovagal baroreflex sensitivity, as estimated during a Valsalva maneuver ( r = 0.54, P < 0.005). In conclusion, regular rowing exercise in middle-aged and older adults is associated with a favorable effect on the elastic properties of the central arteries. Our results suggest that simultaneously performed endurance training may negate the stiffening effects of strength training.

Correction After publication of our paper [1], we discovered that our normalized blood velocity and compliance numbers were 60 times higher than they should have been. The revised Figure 1 and Figure 2, along with Table 1 are shown here with the correct values. Heart rate, blood pressure, and half time to recovery of blood flow and oxygen saturation from the original article are all correct. The statistical analysis and interpretation of the data remain unchanged. We apologize for the error. Published: 08 July 2003

Our purpose was to determine if aging had an influence on muscle blood flow independent of habitual physical activity levels. Blood flow was measured in the femoral artery by Doppler ultrasound after cuff occlusion of 10 minutes. Active and inactive older subjects (73 ± 7 years) were compared to active and inactive young subjects (26 ± 6 years). Peak blood flow capacity when normalized to lean muscle mass was related to activity level (p < 0.001), but not to age. Specifically, the young active group had higher peak blood flows than the young inactive (p = 0.031) or older inactive (p = 0.005) groups. Resting blood flow and conductance were not significantly different between groups. Mean arterial pressure was significantly higher in the older compared to young group (p = 0.002). Conductance was related to both activity (p = 0.002) and age (p = 0.003). A prolonged time for blood flow to recover was found in the older compared to the young group (p = 0.038) independent of activity status. The prolonged recovery time in the older subjects may suggest a reduced vascular reactivity associated with increased cardiovascular disease risk. Peak blood flow capacity is maintained in older subjects by physical activity. In summary, maximal flow capacity and prolonged recovery of blood flow are influenced by different mechanisms in young and older active and inactive subjects.

Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary ( n = 10, 24 ± 2 yr) and middle-aged ( n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young ( n = 9, 25 ± 1 yr) and middle-aged endurance-trained ( n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age.