Citations

The purpose of this study is to examine the effects of a 3-month interval walking program on peak aerobic capacity and cardiovascular risk factors in middle-aged sedentary individuals. Participants were divided into 2 groups: a nontraining control group (n = 17) and an interval walking training group (n = 29). Participants in the interval walking training group were instructed to perform 5 or more sets of 3-min low-intensity walking interspersed by 3-min of moderate to high-intensity walking (>70% of peak aerobic capacity) on 4 or more days/week. Measurements of peak aerobic capacity, blood pressure, blood lipids, and glucose concentration were performed before and after training. Twenty-six individuals completed the interval walking program averaging 4 days/week for 34 min, of which 16 min were moderate to high-intensity walking, with a total energy expenditure of 776 kcal/week. Three months of interval walking increased peak aerobic capacity (from 20.4 ± 3.0 to 26.0 ± 5.2 mL/kg/min; P < .001) and reduced resting systolic blood pressure (127 ± 11 to 119 ± 11 mm Hg; P = .01). There was an inverse correlation between initial level and training-induced changes in glucose, HbA1c, high-density lipoprotein, and low-density lipoprotein. Conversely, 3 months of nontraining did not improve physical fitness or cardiovascular risk factors. Very modest amounts of aerobic exercise involving brief periods of interspersed higher intensity exercise can significantly increase peak aerobic capacity and reduce resting systolic blood pressure in middle-aged sedentary individuals and contribute to a normalization of cardiovascular risk factors in individuals with elevated initial values.

As our understanding of the importance of individualized medicine continues to grow, the clinical relevance of interindividual variability in hemodynamic variables is receiving increasing attention. However, it is not known whether the rat, which is often used for studies of cardiovascular regulation, exhibits similar interindividual variability. In the present study, we evaluated whether the magnitude of interindividual variability in cardiac output (CO) and total peripheral resistance (TPR) was similar in humans and in rats. We assessed interindividual variability of mean arterial pressure (MAP), CO, and TPR during control conditions in normotensive humans ( n = 40) and during normotension and deoxycorticosterone acetate-salt hypertension in Sprague-Dawley rats ( n = 16). Humans and rats showed marked interindividual variability in CO and TPR but low variability in MAP. During deoxycorticosterone acetate-salt hypertension, CO was maintained, but TPR was elevated compared with the baseline period. We conclude that the magnitudes of interindividual variability of MAP, CO, and TPR are quantitatively similar in humans and rats, providing support for the relevance of this variability in both species and suggesting that studies in rats could be designed to address questions specific to individualized medicine in hypertension.

Background— Whether locomotor muscle afferent neural activity contributes to exercise hyperpnea and symptoms of dyspnea in heart failure (HF) is controversial. We examined the influence of metaboreceptor stimulation on ventilation with and without maintaining end-exercise end-tidal CO 2 levels. Methods and Results— Eleven patients with HF aged 51±5 years (ejection fraction, 32±3%; New York Heart Association class, 1.6±0.2) and 11 age- and gender-matched healthy control participants aged 43±3 years were studied. Participants underwent 3 steady-state cycling sessions at 60% of peak oxygen consumption for 4 minutes. The first exercise session was a baseline control trial. Bilateral thigh tourniquets were inflated to suprasystolic pressure at end exercise for 2 minutes during 2 of the trials (regional circulatory occlusion) with the addition of inspired CO 2 to maintain end-exercise partial pressure of end-tidal CO 2 during 1 trial (regional circulatory occlusion+CO 2 ). Minute ventilation was measured continuously throughout each trial. At 2 minutes postexercise during the baseline control trial in patients with HF, minute ventilation was 54% of end exercise, whereas the control group averaged 41% ( P =0.11). During regional circulatory occlusion in patients with HF, minute ventilation was 60% of end exercise; however, the control group averaged 35% ( P <0.001). During regional circulatory occlusion+CO 2 , the minute ventilation of patients with HF averaged 67% of end exercise, whereas the control group averaged 44% ( P <0.001). Conclusion— These data suggest that increased afferent neural activity from the large locomotor muscles associated with metabolites generated during exercise contribute to the augmented ventilatory response to exercise in patients with HF.

Within an individual, diastolic blood pressure (DBP) is negatively related to sympathetic burst incidence, such that lower pressure is associated with high burst incidence. Our goal was to explore the use of a calculation of a DBP “error signal” in the control of muscle sympathetic nerve activity in men and women. Baseline muscle sympathetic nerve activity was measured in healthy young men (n=22) and women (n=28). Women had significantly lower muscle sympathetic nerve activity than men (29±3 versus 43±2 bursts per 100 heartbeats; P <0.05). For each individual, the DBP at which there is a 50% likelihood of a muscle sympathetic nerve activity burst, the “T50” value, was calculated. Mean DBP was subtracted from the T50 blood pressure as an approximate error signal for burst activation. Error signal was negative in both sexes, indicating that DBP in both sexes was higher than the DBP value associated with a 50% burst likelihood. However, average error signal was significantly larger in women (−4±2 mm Hg) than in men (−1±0 mm Hg; P <0.05 versus women). We conclude that women operate at a mean DBP greater than their T50 compared with men, and this may be a contributing factor to low basal muscle sympathetic nerve activity in women. The relationship between error signal and burst incidence may provide important insight into the control of muscle sympathetic nerve activity across sexes and in various populations.

The sensitivity of baroreflex control of sympathetic nerve activity (SNA) represents the responsiveness of SNA to changes in blood pressure. In a slightly different analysis, the baroreflex threshold measures the probability of whether a sympathetic burst will occur at a given diastolic blood pressure. We hypothesized that baroreflex threshold analysis could be used to estimate the sensitivity of the sympathetic baroreflex measured by the pharmacological modified Oxford test. We compared four measures of sympathetic baroreflex sensitivity in 25 young healthy participants: the “gold standard” modified Oxford analysis (nitroprusside and phenylephrine), nonbinned spontaneous baroreflex analysis, binned spontaneous baroreflex analysis, and threshold analysis. The latter three were performed during a quiet baseline period before pharmacological intervention. The modified Oxford baroreflex sensitivity was significantly related to the threshold slope ( r = 0.71, P < 0.05) but not to the binned (1 mmHg bins) and the nonbinned spontaneous baroreflex sensitivity ( r = 0.22 and 0.36, respectively, P > 0.05), which included burst area. The threshold analysis was also performed during the modified Oxford manipulation. Interestingly, we found that the threshold analysis results were not altered by the vasoactive drugs infused for the modified Oxford. We conclude that the noninvasive threshold analysis technique can be used as an indicator of muscle SNA baroreflex sensitivity as assessed by the modified Oxford technique. Furthermore, the modified Oxford method does not appear to alter the properties of the baroreflex.

We previously demonstrated that skeletal muscle blood flow is restored in the exercising forearm during experimental hypoperfusion via local dilator and/or myogenic mechanisms. This study examined the role of nitric oxide (NO) in the restoration of blood flow to the active muscles during hypoperfusion. Eleven healthy subjects (10 men/1 woman; 25 ± 1 yr of age) performed rhythmic forearm exercise (10% and 20% of maximum) while hypoperfusion was evoked by balloon inflation in the brachial artery above the elbow. Each trial included baseline, exercise, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound) and local (brachial artery catheter pressure, BAP) and systemic arterial pressure [mean arterial pressure (MAP); Finometer] were measured. The exercise bouts were repeated during NG-monomethyl-l-arginine (l-NMMA) infusion (NO synthase inhibition). Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from BF (ml/min) and BAP (mmHg). FBF and FVC fell acutely with balloon inflation during all trials ( P < 0.01). Recovery of FBF and FVC [(inflation − nadir)/(steady-state exercise − nadir)] with l-NMMA administration was reduced during 20% exercise (FBF = 77 ± 7% vs. 88 ± 8%; FVC = 71 ± 8% vs. 90 ± 9%; P < 0.01) but not 10% exercise (FBF = 83 ± 4% vs. 81 ± 5%, P = 0.37; FVC = 75 ± 10% vs. 76 ± 7%; P = 0.44) compared with the respective control trial. The time to steady-state vasodilator response was substantially longer during the l-NMMA trials (10% = 74 ± 4 s vs. 61 ± 6 s; 20% = 53 ± 4 s vs. 41 ± 4 s; P < 0.05). Thus the magnitude and timing of the NO contribution to compensatory dilation during forearm exercise with hypoperfusion was dependent on exercise intensity. These observations suggest that NO is released by contracting muscles or that a portion of the dilation caused by ischemic metabolites is NO dependent.

We tested the hypothesis that adenosine contributes to augmented skeletal muscle vasodilation during hypoxic exercise. In separate protocols, subjects performed incremental rhythmic forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O2saturation). In protocol 1 ( n = 8), subjects received an intra-arterial administration of saline (control) and aminophylline (adenosine receptor antagonist). In protocol 2 ( n = 10), subjects received intra-arterial phentolamine (α-adrenoceptor antagonist) and combined phentolamine and aminophylline administration. Forearm vascular conductance (FVC; in ml·min−1·100 mmHg−1) was calculated from forearm blood flow (in ml/min) and blood pressure (in mmHg). In protocol 1, the change in FVC (ΔFVC; change from normoxic baseline) during hypoxic exercise with saline was 172 ± 29 and 314 ± 34 ml·min−1·100 mmHg−1(10% and 20%, respectively). Aminophylline administration did not affect ΔFVC during hypoxic exercise at 10% (190 ± 29 ml·min−1·100 mmHg−1, P = 0.4) or 20% (287 ± 48 ml·min−1·100 mmHg−1, P = 0.3). In protocol 2, ΔFVC due to hypoxic exercise with phentolamine infusion was 313 ± 30 and 453 ± 41 ml·min−1·100 mmHg−1(10% and 20% respectively). ΔFVC was similar at 10% (352 ± 39 ml·min−1·100 mmHg−1, P = 0.8) and 20% (528 ± 45 ml·min−1·100 mmHg−1, P = 0.2) hypoxic exercise with combined phentolamine and aminophylline. In contrast, ΔFVC to exogenous adenosine was reduced by aminophylline administration in both protocols ( P < 0.05 for both). These observations suggest that adenosine receptor activation is not obligatory for the augmented hyperemia during hypoxic exercise in humans.

As humans age, the tonic level of activity in sympathetic vasoconstrictor nerves increases and may contribute to age-related increases in blood pressure. In previous studies in normotensive young men with varying levels of resting sympathetic nerve activity, we observed a balance among factors contributing to blood pressure regulation, such that higher sympathetic activity was associated with lower cardiac output and lesser vascular responsiveness to α-adrenergic agonists, which limited the impact of high sympathetic activity on blood pressure. In the present study, we tested the hypothesis that older normotensive men would exhibit a similar balance among these variables (sympathetic nerve activity, cardiac output, and α-adrenergic responsiveness) but that this balance would be shifted toward higher sympathetic nerve activity values. We measured muscle sympathetic nerve activity, cardiac output, arterial pressure, and forearm vasoconstrictor responses in 17 older men and compared these with previous data collected in 14 younger men. Muscle sympathetic activity (burst incidence) was positively related to diastolic blood pressure in the older men ( r =0.49; P =0.05); this relationship was not observed in young men. In addition, there was no relationship between cardiac output and muscle sympathetic activity ( r =0.29; P >0.05) or between muscle sympathetic activity and vasoconstrictor responses in the older men (eg, norepinephrine: r =−0.21; P >0.05). Although our older subjects were normotensive, the relationship between muscle sympathetic nerve activity and diastolic blood pressure and the lack of “balance” among the other variables suggest that these changes with aging may contribute to the risk of sympathetically mediated hypertension in older humans.

Aging is associated with reduced endothelial function. There is indirect evidence for reduced prostacyclin (PGI 2 )-mediated vasodilation with aging, but it is unknown whether this is because of reduced dilation to PGI 2 or altered production. In addition, the contribution of endothelial NO to PGI 2 -mediated dilation is unknown. Using plethysmography to determine forearm blood flow, we studied the effect of PGI 2 in 10 older (61 to 73 years) and 10 younger (19 to 45 years) subjects using 3 escalating intra-arterial doses of PGI 2 (epoprostenol). PGI 2 was also administered after NO synthase inhibition with N G -monomethyl- l -arginine acetate. The percent of change in forearm vascular conductance (mean±SEM) from baseline after PGI 2 was significantly lower ( P =0.002) in the aging individuals (52±11%, 164±23%, and 221±27% versus 115±20%, 249±19%, and 370±35%). In addition, the group-by-dose interaction was also significant ( P =0.018). After NO synthase inhibition, the dose-response curve to PGI 2 was blunted in the young subjects but unchanged in the older subjects; the difference between the groups was no longer significant. Our data suggest that the reduced dilator effects of PGI 2 in older individuals are attributable to a reduction in the contribution of endothelial-derived NO versus alterations in the direct effects of PGI 2 on vascular smooth muscle.