We tested the hypotheses that smoking-induced changes in vascular mechanics would be detected earlier in the lumped properties of peripheral vascular beds, which include the properties of microvasculature, than in the local properties of central conduits, and that such changes are reversible with lifestyle changes that include smoking cessation and exercise. Vascular measures were made in 53 young (18-40 years) female smokers and 25 age-matched non-smokers. Twenty-two of the smokers were tested before and after a 14-week smoking cessation program and, of these, 13 were tested again after 52 weeks of smoking cessation. Compared with non-smokers, lumped forearm vascular bed compliance (C: mL/mm Hg) was lower, while lumped viscoelasticity (K: mm Hg/(mL·min)) and resistance (R: mm Hg/(mL·min)) were higher in the smoker group. Neither the carotid-to-toe pulse wave velocity nor local carotid artery elasticity indices were different between groups. Compared with non-smokers, brachial artery distensibility was less, and other markers of stiffness higher, in the smoker group. At 14 and 52 weeks of smoking cessation, forearm vascular R was reduced and C was increased while K was unchanged. The changes in C and R occurred while maintaining a constant R×C value, which represents a dynamic time constant. Thus, early changes in K were observed in the forearm vascular bed of smokers, which were not reflected in the local properties of central conduit vessels. Forearm C, but not K, was reversed following smoking cessation, a finding that may represent a persistent effect of smoking on the intercellular matrix of the vessel wall.

This study tested the hypothesis that long‐term endurance training (ET) preserves cardiovagal control in aging individuals. Baroreflex sensitivity (BRS) and the rapid heart rate response at exercise onset (ΔHR) reflect levels of cardiovagal control. BRS declines with age and cardiovascular disease but, reportedly, this effect can be reversed by ET. It remains unclear if ET also preserves ΔHR (reflecting removal of parasympathetic cardiac inhibition). Both BRS (sequence method, 5–10 min of baseline) and ΔHR to three, 30s contractions at 40% of their maximum voluntary contraction strength, were assessed in a group of young individuals (Y; age=26±4) and in groups of older individuals who were healthy (O; age=56±4), endurance trained (ET; age=55±4) or entering cardiac rehabilitation (CR; age=59±4) (n=15 for each group). Compared with Y (10±9 bpm), ΔHR was less in CR (3±2 bpm; P<0.05) but not the other groups (O: 7±5, ET: 5±3 bpm; NS). Similarly, compared with Y (30±15 ms/mmHg), BRS was less in CR (14±12 ms/mmHg) but not the other groups (O: 20±12, ET: 25±15 ms/mmHg). Contrary to previous results, ET did not preserve BRS at levels expressed in Y. However, age correlated strongly with BRS and ΔHR (r=−0.4, p=0.001; r=−0.3, p=0.013 respectively) across all groups. The results suggest that age exerts a dominant impact on cardiovagal control and that this effect remains difficult to restore with long‐term ET. Supported by CIHR.

The present study was designed to address the contribution of α‐adrenergic modulation to the genesis of low‐frequency (LF; 0.04–0.15 Hz) oscillations in R–R interval (RRi), blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during different sympathetic stimuli. Blood pressure and RRi were measured continuously in 12 healthy subjects during 5 min periods each of lower body negative pressure (LBNP; −40 mmHg), static handgrip exercise (HG; 20% of maximal force) and postexercise forearm circulatory occlusion (PECO) with and without α‐adrenergic blockade by phentolamine. Muscle sympathetic nerve activity was recorded in five subjects during LBNP and in six subjects during HG and PECO. Low‐frequency powers and median frequencies of BP, RRi and MSNA were calculated from power spectra. Low‐frequency power during LBNP was lower with phentolamine versus without for both BP and RRi oscillations (1.6 ± 0.6 versus 1.2 ± 0.7 ln mmHg2, P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms2, P = 0.001, respectively). In contrast, the LBNP with phentolamine increased the power of high‐frequency oscillations (0.15–0.4 Hz) in BP and MSNA (P < 0.01 for both), which was not observed during saline infusion. Phentolamine also blunted the increases in the LBNP‐induced increase in frequency of LF oscillations in BP and RRi. Phentolamine decreased the LF power of RRi during HG (P = 0.015) but induced no other changes in LF powers or frequencies during HG. Phentolamine resulted in decreased frequency of LF oscillations in RRi (P = 0.004) during PECO, and a similar tendency was observed in BP and MSNA. The power of LF oscillation in MSNA did not change during any intervention. We conclude that α‐adrenergic modulation contributes to LF oscillations in BP and RRi during baroreceptor unloading (LBNP) but not during static exercise. Also, α‐adrenergic modulation partly explains the shift to a higher frequency of LF oscillations during baroreceptor unloading and muscle metaboreflex activation.

Orthostatic challenge increases total peripheral resistance (TPR) which is not completely explained by α-adrenergic control. It is not known whether non-α-adrenergic mechanisms are involved during exercise. Twelve healthy subjects underwent lower-body negative pressure LBNP (5 min, −40 mmHg) and static handgrip exercise HG (5 min, 20% of MVC) followed by post-exercise circulatory occlusion (PECO, 5 min) with and without α-adrenergic blockade by phentolamine (PHE). Aortic blood flow and finger blood pressure were measured to calculate cardiac output (Q) and TPR during the last minute of each intervention. LBNP resulted in a greater reduction in Q with PHE than without PHE (p<0.05). Response in Q was larger during HG and PECO with PHE than without PHE (p<0.05, for both). TPR increased similarly during LBNP with and without PHE (+6.2±5.3 vs. +3.6±3.3 L/min/mmHg, p=0.110). In contrast, PHE abolished the increases in TPR during HG (+3.1±4.0 vs. −0.8±3.4 L/min/mmHg, p<0.001) and PECO (+6.5±7.9 vs. +0.3±3.9 L/min/mmHg, p=0.005). These data suggest that while α-adrenergic control is not responsible for increasing TPR during LBNP, α-adrenergic inhibition blunts the responses in TPR during prolonged 5-min model of static handgrip exercise and muscle metaboreflex activation. Supported by Academy of Finland, TEKES Finland, Canadian Institutes of Health Research and Finnish Foundation of Cardiovascular Research

Sympathetic nerve activity is an important regulator of blood pressure and blood flow in humans. Our understanding about how sympathetic neurons are recruited during baroreflex stress is limited. This paper investigates the sympathetic neural recruitment patterns during the Valsalva maneuver. Using microneurography, muscle sympathetic nerve activity was recorded in seven healthy subjects during baseline and the Valsalva maneuver. A new algorithm for detection and classification of action potentials was employed to study the differences between the recruitment of sympathetic neurons during baseline and the Valsalva maneuver. The data suggests that the Valsalva maneuver increases the number of spikes per sympathetic bursts and also recruits at least one additional new cluster of larger, faster conducting neurons. Also, action potential's latencies (i.e., inverse of conduction velocity) were shifted downward for all action potential clusters during this maneuver.

The within-breath modulation of muscle sympathetic nerve activity (MSNA) is well established, with greater activity occurring during expiration and less during inspiration. Whether ventilation per se affects the longer-term (i.e., minute-to-minute) regulation of MSNA has not been determined. We sought to define the specific role of ventilation in regulating sympathetic activation during chemoreflex activation, where both ventilation and MSNA are increased. Ten young healthy subjects performed both asphyxic rebreathing and repeated, rebreathing apneas to cause the same magnitude of chemoreflex stress in the presence or absence of ventilation. Both protocols caused increases in sympathetic burst frequency, burst amplitude, and burst incidence. However, burst frequency was increased more during repeated apneas (12 ± 6 to 25 ± 7 bursts/min) compared with rebreathing (12 ± 5 to 17 ± 7 bursts/min; P < 0.001) due to a greater burst incidence during apneas (36 ± 11 bursts/100 heart beats) vs. rebreathing (26 ± 8 bursts/100 heart beats, P < 0.001). The sympathetic gain to chemoreflex stress was also larger during repeated apneas (2.29 ± 1.29 au/% desaturation) compared with rebreathing (1.44 ± 0.53 au/% desaturation, P < 0.05). The augmented sympathetic response during apneas was associated with a larger pressor response and total peripheral resistance compared with rebreathing. These data demonstrate that ventilation per se restrains sympathetic activation during chemoreflex activation. Further, the augmented sympathetic response during apneas was associated with greater cardiovascular stress and may be relevant to the cardiovascular pathology associated with sleep-disordered breathing.

The purpose of this study was to assess the power and the frequency of low-frequency (LF; 0.04–<0.15Hz) oscillations in systolic blood pressure (SBP) and R–R interval (RRi) across the continuum of risk of cardiovascular disease, including age. A potential confound in such determinations is low spontaneous breathing frequency in some individuals. We measured beat-to-beat SBP, RRi and respiration in healthy YOUNG (33±3years) and OLDER subjects (62±5years) and older patients with hypertension (HT, 61±5years), coronary artery disease without (CAD, 62±5years) and with type 2 diabetes (CAD+DM, 62±4years, n=28 for all groups) during spontaneous breathing at supine rest. Power (PowerLF) and median frequency (MedLF) of LF oscillations were calculated by power spectral analysis after removing respiratory effects by least-mean-square adaptive filtering. OLDER had higher PowerLF-SBP (5.5±3.0 vs. 3.4±2.5mmHg2, p=0.002) and lower PowerLF-RRi than YOUNG (339±460 vs. 575±422ms2, p=0.001) whereas neither variable differed between OLDER and patient groups. MedLF-SBP (0.072±0.009 vs. 0.080±0.011Hz, p=0.005) and MedLF-RRi (0.072±0.010 vs. 0.079±0.013Hz, p=0.027) were lower in OLDER compared with YOUNG. Compared with OLDER, MedLF-RRi was lower in CAD (0.065±0.006Hz, p=0.015) and CAD +DM (0.066±0.008Hz, p=0.012); whereas CAD+DM had also lower MedLF-SBP (0.065±0.006Hz, p=0.012). No differences were observed between OLDER and HT and between CAD and CAD+DM in these variables. We concluded that age is major determinant of the power of LF oscillations in SBP and RRi at rest, whereas the median frequency of these oscillations is altered also by coronary artery disease.

Low‐frequency (LF, 0.04‐0.15 Hz) oscillations of arterial pressure are associated to sympathetic activity. We measured beat‐to‐beat systolic blood pressure (SBP) and respiration for YOUNG (n=39, 34±3 yrs) and OLD (n=40, 64±6 yrs) healthy subjects and patients with hypertension (HT, n=38, 60±7 yrs), coronary artery disease (CAD, n=16, 61±4 yrs) and diabetes (CAD+DM, n=29, 60±6 yrs) at supine rest. Spectral power (LFSBPpower) and center frequency (LFSBPf) of SBP oscillations within LF band were calculated. Adaptive filtering was applied to reduce the effects of slow breaths on SBP oscillations at LF. Significant group‐effects were found in LFSBPpower (YOUNG: 4.0±2.5, OLD 6.1±3.4, HT: 5.2±3.3, CAD: 4.2±2.6 and CAD+DM: 4.1±3.0 mmHg2, p=0.014) and LFSBPf (YOUNG: 0.073±0.015, OLD: 0.064±0.011, HT: 0.068±0.011, CAD: 0.054±0.007 and CAD+DM: 0.056±0.010 Hz, p<0.001). OLD had higher LFSBPpower (p=0.003) and lower LFSBPf (p=0.008) than YOUNG. LFSBPpower and LFSBPf did not differ between OLD and HT, whereas CAD had lower LFSBPf (p<0.001) and tended to have lower LFSBPpower (p=0.050) than OLD. No differences were found in LFSBPpower and LFSBPf between CAD and CAD+DM. We concluded that LF arterial pressure oscillations at resting condition are affected by age and cardiac disease but appear to be unaffected by diabetes in cardiac patients or by hypertension. Supported by Academy of Finland, TEKES Finland and CIHR.

The dynamics of blood supply to a vascular bed depend on lumped mechanical properties of that bed, namely the compliance (C), resistance (R), viscoelasticity (K), and inertance (L). While the study of regulatory mechanisms has so far placed the emphasis largely on R, it is not known how the remaining properties contribute collectively to the play of dynamics in vasomotor control. To examine this question and to establish some benchmark values of these properties, simultaneous measurements of pressure and flow waveforms in the vascular bed of the forearm were obtained from three groups: young healthy individuals, older hypertensives with controlled blood pressure, and older hypertensives with uncontrolled blood pressure. The values of R and C were found to vary within a wide range in each of the three groups to the extent that neither R nor C could be used independently as an indicator of health or age of the subjects tested. However, higher level dynamic properties of the bed, such as the time constants and damping index, which depend on combinations of C, K, and L, and which may reflect measures of the dynamic responsiveness or "sluggishness" of the system, were found to be maintained over a wide range of pulse pressures. These findings support a hypothesis that the pulsatile dynamics of blood supply to a vascular bed are adapted to the individual baseline values of R and C in different subjects with the effect of optimizing the level of dynamic responsiveness to changes in pressure or flow, and that this dynamic property of the vascular bed may be a protected and/or regulated property.

An emerging hypothesis states that vascular disease is initiated within the microvasculature. Using a modified Windkessel model, lumped mechanical properties of the forearm vascular bed were examined to determine the effect of chronic hypertension on the blood supply to skeletal muscle. Systemic pulse pressure (PP; Finometer), brachial artery radius (BAR; Ultrasound), vascular bed compliance (C), and resistance (R) were measured in (I), Hypertensive (HT) patients with controlled blood pressure (CBP) and high glucose (HG)(n=8), (II) HT patients with CBP and normal glucose (NG)(n=10), (III) HT patients with uncontrolled blood pressure (UBP) and HG (n=18), (IV) HT patients with UBP and NG (n=16), and (V) age‐matched, healthy controls (n=27). R was decreased and BAR was increased in UBP groups with HG levels compared to all other groups (p<0.05). PP was found to vary across groups, but was unrelated to C. These findings support a model of systolic HT which is consistent with the PP results. UBP with high glucose appears to initiate hypertrophic remodelling leading to reduced vascular R. However, from a vascular mechanics perspective, hypertension, with or without high glucose, does not modify microvascular compliance in skeletal muscle. Supported by Canadian Institutes of Health Research, NSERC, and the Canadian Diabetes Association.

Elevated cardiac output (Q) during isometric contractions may be due to neural signals arising from the motor cortex or from the contracting muscle. This study tested the hypothesis that skeletal muscle sensory inputs affect cardiac function and that this effect depends on baroreceptor loading. Three‐minute segments of heart rate (HR; ECG), mean arterial pressure (MAP), and Q (Finometer) were obtained during supine rest, ‐35 mmHg lower body negative pressure (LBNP), and LBNP + electrical stimulation (ES) of the forearm (n=7 males). ES was applied at sub‐motor (group I and II afferents) and non‐fatiguing supra‐motor threshold (group III and IV fibers) levels. Parasympathetic indicators were assessed by heart rate variability (HRV) analysis. ES had no effect on HR, MAP, Q or HRV during supine rest. LBNP increased HR and decreased pulse pressure (P<0.05). Q during LBNP was reduced further with sub‐motor ES versus LBNP (‐0.142 L/min; P<0.05). Compared with LBNP alone, Q was increased during LBNP + supra‐motor ES (+0.132 L/min; P<0.05). ES during LBNP did not change HR, MAP, or HRV indicators. These results suggest that Type I and II afferents depress, and Type III and IV afferents augment Q during LBNP. As indices of HRV and parasympathetic outflow were not affected, these data suggest that muscle afferent stimulation affects Q through a sympathetic neural mechanism. Supported by the Heart and Stroke Foundation of Ontario.

During the first minute of a moderate-intensity isometric handgrip (HG) exercise, there is an increase in stroke volume and cardiac output that occurs without any change in systemic vascular conductance. Although the mechanism of increased venous return is not yet known, current focus has been placed on the constriction of visceral organs. The human spleen represents a compliant organ with high perfusion that constricts during the rather severe stresses of maximal exercise, a diving reflex, or prolonged apnea. This study tested the hypothesis that spleen constriction occurs during isometric HG exercise. Eight participants performed a 1 min isometric HG test at 40% maximum voluntary contraction. Splenic length and width were measured (with ultrasound imaging) after 1 min of exercise, and volume was calculated. To investigate the reflex specificity of this response, spleen dimensions were also measured during 4 min of lower-body negative pressure (LBNP; -20 mm Hg). To test the additional impact of altered breathing and intra-abdominal pressures during the HG, measures were also taken during Valsalva's manoeuvre (VM) at 30 mm Hg. Compared with baseline, both length and width of the spleen were reduced by 0.20 to 0.55 cm (or 4.44%-6.09%; p < 0.05) during each test. This resulted in relative reductions in splenic volume of 13 +/- 1% (HG), 9% +/- 7% (LBNP) and 18% +/- 7% (VM) (p < 0.05; all mean +/- SD). It was concluded that the spleen can constrict during the first minute of isometric HG exercise.

The relationship between arterial stiffness and cardiovascular disease has been implicated in the development of isolated systolic hypertension. This study tested the hypothesis that hypertension is related to altered vascular mechanics and hence altered hemodynamics in skeletal muscle. The ability to detect such changes was tested using a lumped Windkessel model that incorporates several parameters of vascular control including resistance (R), compliance (C), viscoelasticity (K) and inertance (L). Two groups of middle aged hypertensive individuals were tested, one with normal blood pressure (NBP) following treatment (n=10), and the other with uncontrolled BP (UBP) (n=27). Baseline beat‐by‐beat measures of heart rate (ECG), mean arterial BP (Finometer), and forearm blood flow (FBF; Doppler ultrasound) were collected. Systolic BP, pulse pressure and mean arterial pressure were higher in the UBP group (p<0.01). Furthermore, values of C (0.008 for NBP vs. 0.006 mL/mmHg for UBP; p<0.02) and K (0.161 for NBP vs. 0.233 mmHg/mL/min for the UBP group; p=0.1) indicated that indeed the vessel walls in the UBP group were less compliant and offered more viscous resistance to stretch. Values of R were the same in the two groups. These findings suggest that hypertensive individuals with controlled BP are better able to maintain the function of skeletal muscle vasculature for muscle perfusion. Supported by the Heart & Stroke Foundation of Canada and the Canadian Stroke Network.