Exercise-induced sympathetic activation is correlated with cerebral hemisphere laterality, but not handedness

To investigate whether sympathetic responses are correlated with central laterality or handedness, muscle sympathetic nerve activity (MSNA), heart rate (HR) and blood pressure (BP) were compared between right (RA) and left arm (LA) grip exercise with volitional maximum effort (MVHG) for 2 min and post-exercise arterial occlusion (PEAO) in right- and left-handed volunteers. MVHG and PEAO led to a greater increase in MSNA in RA than in LA exercise (180 vs. 150%, P=0.004; 140 vs. 85%, P=0.005). MVHG elevated HR to a significantly lesser extent in RA than in LA (35 vs. 46%, P=0.030), and the difference was maintained during PEAO. The BP rise during MVHG and PEAO was the same in RA and in LA. Muscle sympathetic nerve activity, HR and BP responses during MVHG and PEAO showed no difference between the dominant and non-dominant arm. These results suggested that the effects of central motor command and metaboreflex on sympathetic outflow to the vasculature and the heart may be selectively modulated partly by hemispherical laterality.     

Changes in muscle sympathetic nerve activity and calf blood flow during combined leg and forearm exercise

In order to examine efferent sympathetic nerve control of the peripheral circulation during exercise, muscle sympathetic nerve activity (MSNA), calf blood flow (CBF), heart rate (HR), blood pressure (BP) and oxygen uptake were measured during combined foot and forearm exercise. An initial period of rhythmic foot exercise (RFE) (60 min^-1 at 10% of maximal voluntary contraction (MVC) was followed by the addition of rhythmic handgrip exercise (RFE+OCCL) (60 min at 30% of MVC) and by forearm ischaemia after handgrip exercise while continuing RFE (RFE + OCCL). During RFE, CBF in the working leg, HR and oxygen increased respectively by 560%, 121% and 144% when compared with the control rest period, but MSNA (burst rate) was reduced by 13% (P > 0.05) and BP was unchanged. During RFE+RHG, HR, BP and oxygen uptake were greater than during RFE alone. There was no change in CBF, but a significant increase occurred in calf vascular resistance (CVR) and MSNA increased to 121% of the control level. During RFE + OCCL, MSNA, CVR and BP were all higher than during RFE alone, whereas HR and oxygen uptake decreased slightly, although they remained higher than the control values. The increase in CVR in the working leg and the rise in BP during RFE+RHG or RFE+OCCL might be linked to enhancement of MSNA, which may have been reflexly evoked by input from muscle metabolic receptors in the working forearm.     

Changes in muscle sympathetic nerve activity and calf blood flow during combined leg and forearm exercise.

In order to examine efferent sympathetic nerve control of the peripheral circulation during exercise, muscle sympathetic nerve activity (MSNA), calf blood flow (CBF), heart rate (HR), blood pressure (BP) and oxygen uptake were measured during combined foot and forearm exercise. An initial period of rhythmic foot exercise (RFE) (60 min-1 at 10% of maximal voluntary contraction (MVC) was followed by the addition of rhythmic handgrip exercise (RFE + OCCL) (60 min at 30% of MVC) and by forearm ischaemia after handgrip exercise while continuing RFE (RFE + OCCL). During RFE, CBF in the working leg, HR and oxygen increased respectively by 560%, 121% and 144% when compared with the control rest period, but MSNA (burst rate) was reduced by 13% (P > 0.05) and BP was unchanged. During RFE + RHG, HR, BP and oxygen uptake were greater than during RFE alone. There was no change in CBF, but a significant increase occurred in calf vascular resistance (CVR) and MSNA increased to 121% of the control level. During RFE + OCCL, MSNA, CVR and BP were all higher than during RFE alone, whereas HR and oxygen uptake decreased slightly, although they remained higher than the control values. The increase in CVR in the working leg and the rise in BP during RFE + RHG or RFE + OCCL might be linked to enhancement of MSNA, which may have been reflexly evoked by input from muscle metabolic receptors in the working forearm.     

Sympathetic and cardiovascular activity during cataplexy in narcolepsy

Autonomic nervous system activity changes have been described during cataplexy as playing a role in triggering it. To confirm these previous findings, we investigated the time course of sympathetic and cardiovascular activities during cataplexy. We made for the first time microneurographic recordings of 10 cataplectic episodes in three patients with hypocretin‐deficient narcolepsy. During microneurography, muscle sympathetic nerve activity (MSNA) was recorded simultaneously with heart rate (HR), respiratory movements, arterial finger blood pressure (BP), electroencephalography, electro‐oculogram and superficial electromyogram. Results showed no significant autonomic changes before the onset of the cataplectic episodes. Cataplexy was associated with a significant increase in MSNA and BP compared with baseline, whereas HR was markedly decreased. An irregular breathing pattern mainly characterized by apnea typically occurred during the attacks. In conclusion, our findings did not show significant changes in autonomic activity prior to cataplexy onset, ruling out a triggering role of the autonomic system. However, cataplexy was associated with co‐activation of sympathetic and parasympathetic autonomic systems, a pattern reminiscent of that reported during the vigilance reaction in animals.     

Initiation of increase in muscle sympathetic nerve activity delay during maximal voluntary contraction

To investigate the effects of maximal voluntary exercise on sympathetic nerve activity, contraction force and muscle sympathetic nerve activity (MSNA) were recorded during maximal (MVG) and submaximal voluntary isometric handgrip (SVG) for 2 min in eight healthy subjects. MSNA was determined by a microneurographic technique, and handgrip force, heart rate (HR) and arterial blood pressure (ABP) were measured by a non-invasive method during exercise. Grip force decayed rapidly to 58% of maximal grip force (MGF) at 10 s after commencement of exercise and was almost constant (≈ 30% of MGF) 40 s after exercise. MSNA increase was delayed by 20 s during MVG, followed by a gradual increase. HR was elevated immediately after onset of exercise, while mean ABP rise showed a 20 s lag from initiation of MVG exercise. During SVG increases in MSNA, HR and mean ABP were delayed by 50, 40 and 20 s, respectively, relative to commencement of exercise. Thereafter, these parameters increased time-dependently. These results suggested that the MSNA increase during MVG may be predominantly because of the metaboreflex.     

Local heat application to the leg reduces muscle sympathetic nerve activity in human

The study was designed to assess the effects of local heat (LH) application on postganglionic muscle sympathetic nerve activity (MSNA) measured by microneurography in healthy men. In the first protocol, MSNA of the left peroneal nerve, blood pressure (BP), heart rate (HR), and skin temperature of the shin (TSK) were recorded in nine men. In the second protocol, leg blood flow (LBF) was measured in the same subjects by strain-gauge plethysmography. In both protocols, after 10 min of rest in the supine position, a heated hydrocollator pack was applied to the shin and anterior foot for 15 min and recovery was monitored over a period of 20 min. TSK gradually increased from 31.7 ± 0.1 to 41.9 ± 0.5°C (mean ± SEM) during LH. No subject complained of pain, and BP and HR remained constant. The MSNA burst rate (16.1 ± 2.1 beats/min) during the control period decreased significantly (P < 0.05) to 72.0 ± 2.3% during LH. Total MSNA also decreased to 59.2 ± 2.6% (P < 0.05) during LH, but both immediately returned to baseline at recovery. In contrast, LBF in the left leg significantly and immediately increased (P < 0.05) after LH application and remained significantly elevated until the end of the recovery period. These results suggest that: (1) LH application significantly attenuates MSNA without any changes in HR and BP. (2) Other factors in addition to MSNA seem to control regional blood flow in the lower extremity during LH.     

Comparison of muscle sympathetic nerve activity during exercise in dominant and nondominant forearm

Summary To determine whether or not muscle endurance training alters exercise-induced sympathetic nerve response, we recorded muscle sympathetic nerve activity (MSNA) microneurographically during forearm exercise and compared MSNA between dominant (D) and nondominant (ND) forearms of players of racket sports. Three kinds of forearm exercise were conducted on each side; static (SHG) and dynamic (DHG, at a rate of 1 Hz) handgrip exercise at a loading of 25°10 of maximal voluntary contraction until exhaustion, and 10-min submaximal dynamic handgrip (at a rate of 1 Hz) at an intensity of 0.9 W. Heart rate, ventilation and blood pressure were also monitored at rest and during SHG and DHG exercises. During the last minute of SHG exercise, MSNA burst rate had increased on average by 290 (SEM 46) % in D and 330 (SEM 46) % in ND, while during DHG it increased by 288 (SEM 38) % in D and 344 (SEM 36) % in ND, respectively. There were no significant differences in the MSNA responses between D and ND forearms in either exercise modes. Significant increases in heart rate, ventilation and blood pressure during the last minute of fatiguing SHG and DHG were observed, but there were no significant differences between the two forearms. During submaximal DHG, while MSNA increased significantly above control values in both D and ND, the MSNA response was less in D than that in ND forearm. The results would suggest that exercise-induced MSNA responsiveness is influenced little by muscle endurance training but the intensity of response may be due to the magnitude of metaboreceptor stimulation in the exercising muscle.     

α-Adrenergic effects on low-frequency oscillations in blood pressure and R-R intervals during sympathetic activation

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 mmHg(2), P = 0.049; and 6.9 ± 0.8 versus 5.4 ± 0.9 ln ms(2), 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.     

Middle cerebral artery blood velocity,arterial diameter and muscle sympathetic nerve activity during post-exercise muscle ischaemia

During exercise the transcranial Doppler determined mean blood velocity (V_mean) increases in the middle cerebral artery (MCA) and reflects cerebral blood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate V_mean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether V_mean relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 ± 20 to 92 ± 21 beats min^?1 and mean arterial pressure (MAP) from 87 ± 7 to 105 ± 9 mmHg (mean ± SD; P < 0.05). During PEMI, HR returned to pre-exercise levels while MAP remained elevated (101 ± 9 mmHg). During handgrip contralateral MCA V_mean increased from 65 ± 10 to 75 ± 13 cm s^?1 and this was more than on the ipsilateral side (from 63 ± 10 to 68 ± 10 cm s^?1; P < 0.05). On both sides of the brain V_mean returned to baseline during PEMI. MSNA did not increase significantly during handgrip (from 56 ± 24 to 116 ± 39 units) but the elevation became statistically significant during PEMI (135 ± 86 units, P < 0.05), while AD did not change. Taken together, during exercise and PEMI, V_mean changed independent of an elevation of MSNA by more than 140% and the dorsalis pedis artery diameter was stable. The results provide no evidence for a vasoconstrictive influence of sympathetic nerve activity on medium size arteries of the limbs and the brain during rhythmic handgrip and post-exercise muscle ischaemia.     

Forebrain organization representing baroreceptor gating of somatosensory afferents within the cortical autonomic network

Somatosensory afferents are represented within the cortical autonomic network (CAN). However, the representation of somatosensory afferents, and the consequent cardiovascular effects, may be modified by levels of baroreceptor input. Thus, we examined the cortical regions involved with processing somatosensory inputs during baroreceptor unloading. Neuroimaging sessions (functional magnetic resonance imaging [fMRI]) recorded brain activity during 30 mmHg lower-body negative pressure (LBNP) alone and combined with somatosensory stimulation (LBNP+SS) of the forearm (n = 14). Somatosensory processing was also assessed during increased sympathetic outflow via end-expiratory apnea. Heart rate (HR), blood pressure (BP), cardiac output (Q), and muscle sympathetic nerve activity (MSNA) were recorded during the same protocols in a separate laboratory session. SS alone had no effect on any cardiovascular or MSNA variable at rest. Measures of HR, BP, and Q during LBNP were not different compared with LBNP+SS. The rise in MSNA burst frequency was attenuated during LBNP+SS versus LBNP alone (8 vs. 12 bursts/min, respectively, P < 0.05). SS did not affect the change in MSNA during apnea. Activations within the insula and dorsal anterior cingulate cortex (ACC) observed during LBNP were not seen during LBNP+SS. Anterior insula and ACC activations occurring during apnea were not modified by SS. Thus, the absence of insular and dorsal ACC activity during LBNP+SS along with an attenuation of MSNA burst frequency suggest sympathoinhibitory effects of sensory stimulation during decreased baroreceptor input by a mechanism that includes conjoint insula-dorsal ACC regulation. These findings reveal that the level of baroreceptor input influences the forebrain organization of somatosensory afferents.     

Ageing reduces sympatho-suppressive response to head-out water immersion in humans

Muscle sympathetic nerve activity (MSNA) is suppressed during thermoneutral head-out water immersion (HOI) in humans. In this study, the effects of ageing on the suppressive response of MSNA to HOI were determined. MSNA was recorded microneurographically from the tibial nerve in 16 healthy men, 10 of whom were aged 19–30 years (young group) and six aged 45–67 years (older group). MSNA was suppressed in all the subjects during HOI. The suppressive response was significantly less prominent in the older group than in the young group. A significant negative correlation between age and the suppressive response of MSNA induced by HOI (r=-0.53, P<0.05) was found. We conclude that suppressive response of sympathetic nerve activity to HOI is reduced with age.     

Effects of deep and superficial experimentally induced acute pain on muscle sympathetic nerve activity in human subjects

Human studies conducted more than half a century ago have suggested that superficial pain induces excitatory effects on the sympathetic nervous system, resulting in increases in blood pressure (BP) and heart rate (HR), whereas deep pain is believed to cause vasodepression. To date, no studies have addressed whether deep or superficial pain produces such differential effects on muscle sympathetic nerve activity (MSNA). Using microneurography we recorded spontaneous MSNA from the common peroneal nerve in 13 awake subjects. Continuous blood pressure was recorded by radial arterial tonometry. Deep pain was induced by intramuscular injection of 0.5 ml hypertonic saline (5%) into the tibialis anterior muscle, superficial pain by subcutaneous injection of 0.2 ml hypertonic saline into the overlying skin. Muscle pain, with a mean rating of 4.9 ± 0.8 ( s.e.m. ) on a 0–10 visual analog scale (VAS) and lasting on average 358 ± 32 s, caused significant increases in MSNA (43.9 ± 10.0%), BP (5.4 ± 1.1%) and HR (7.0 ± 2.0%) – not the expected decreases. Skin pain, rated at 4.9 ± 0.6 and lasting 464 ± 54 s, also caused significant increases in MSNA (38.2 ± 12.8%), BP (5.1 ± 2.1%) and HR (5.6 ± 2.0%). The high-frequency (HF) to low-frequency (LF) ratio of heart rate variability (HRV) increased from 1.54 ± 0.25 to 2.90 ± 0.45 for muscle pain and 2.80 ± 0.52 for skin pain. Despite the different qualities of deep (dull and diffuse) and superficial (burning and well-localized) pain, we conclude that pain originating in muscle and skin does not exert a differential effect on muscle sympathetic nerve activity, both causing an increase in MSNA and an increase in the LF : HF ratio of HRV. Whether this holds true for longer lasting experimental pain remains to be seen.     

非接触标测和频谱分析迷走神经介导的心房颤动

目的： 对在体犬迷走神经介导的心房颤动（房颤）进行非接触标测和频谱分析，以探讨其发生和维持机制。方法: 测定8只犬基础情况及双侧迷走神经刺激时心房有效不应期及其离散度，非接触标测和频谱分析房颤时左、右房的电活动。结果: 迷走神经刺激与基础情况相比，左、右心房有效不应期缩短，但有效不应期离散度增大仅见于左房。迷走神经刺激时房颤易诱发和维持，房颤显示反复有序的激动经优先传导路径传播仅见于左房；频谱分析显示左房的主导频谱高于右房［（12.5±1.5)Hz vs (9.3 ±1.2) Hz，P<0.05］。停止迷走神经刺激，左、右房房颤频谱降低［（9.2±0.5)Hz vs (8.5±0.6)Hz， P>0.05］，房颤自发终止。结论: 左、右房电生理特性改变、激动模式差异以及频谱梯度提示迷走神经介导的房颤发生和维持依赖于左房。     

Changes in blood pressure and muscle sympathetic nerve activity during water drinking in humans

To investigate the possible involvement of the sympathetic nervous system in pressor response during water drinking, muscle sympathetic nerve activity (MSNA), blood pressure (BP), and heart rate (HR) were continuously measured in healthy young volunteers throughout the experiments of a 5-min control, 2 min of drinking 500 ml water, and a 28-min recovery. To avoid the effects of water passing through the oropharyngeal and esophageal regions and/or effects of swallowing, an equal amount of water was directly infused to the stomach through a stomach tube for 2 min. Water drinking caused a transient increase in mean arterial pressure (MAP) and HR immediately after drinking (DeltaMAP, 12.6 +/- 2.1 mmHg; DeltaHR, +19.9 +/- 1.7 beats/min at the peak). An abrupt decrease of MSNA was observed directly during water drinking (Deltaburst rate, -6.9 +/- 1.3 bursts/min; Deltatotal activity, -2,606 +/- 491 U/min), and it increased to the baseline level thereafter. Gastric infusion had little or no effect on MAP, HR, and MSNA. The present study demonstrated that a pressor response during water drinking was associated with the attenuation of MSNA and not generated by gastric infusion of water at the same rate as in this drinking manner. In conclusion, the rapid rise in BP might be caused through stimulations from the oropharyngeal region, swallowing-induced factors, and/or a feedforward mechanism by a central descending signal from the higher brain centers.     

Identification of sites of sympathetic outflow at rest and during emotional arousal: Concurrent recordings of sympathetic nerve activity and fMRI of the brain

The sympathetic nervous system subserves many of the autonomic responses to mental stress and emotional processing. While peripheral markers of sympathetic activity can be obtained indirectly – by measuring heart rate, blood pressure, sweat release and skin blood flow – these effector-organ responses are slower compared to the directly recorded sympathetic nerve activity. Microneurography, in which a tungsten microelectrode is inserted percutaneously into a peripheral nerve in awake human subjects, allows one to record sympathetic nerve activity to either muscle or skin. Muscle sympathetic nerve activity (MSNA) is involved in the beat-to-beat control of blood pressure, and is elevated during mental stress; chronic stress can lead to high blood pressure. The primary role of skin sympathetic nerve activity (SSNA) is to regulate body temperature by controlling sweat release and skin blood flow, but it has also been commandeered for emotional expression. In this review we discuss our recent work in which we have performed concurrent microelectrode recordings of MSNA or SSNA and fMRI of the brain, with a view to identifying areas in the brain responsible for generating the increases in sympathetic outflow at rest and during emotional engagement. Spontaneous bursts of MSNA at rest were positively correlated to activity in the left dorsomedial hypothalamus and left insula, and bilaterally in the ventromedial hypothalamus, dorsolateral prefrontal cortex, posterior cingulate cortex and precuneus. Spontaneous bursts of SSNA at rest were positively correlated with activity in the left ventromedial nucleus of the thalamus, the left posterior and right anterior insula, the right orbitofrontal and frontal cortices and bilaterally in the mid-cingulate cortex and precuneus. Increases in SSNA occurred when subjects viewed emotionally charged images, resulting in increases in activity in the central and lateral amygdala, dorsolateral pons, thalamus, nucleus accumbens, and cerebellar cortex; surprisingly, there was no activation of the insula in response to these emotional stimuli. We have shown that concurrent microelectrode recordings of sympathetic outflow to either muscle or skin and fMRI of the brain can be used to identify areas of the brain involved in the generation of sympathetic nerve activity. We propose that this approach can be extended to examine specific disorders of emotional expression to increase our understanding of the underlying neural processes.     

Differences in muscle sympathetic nerve response to isometric exercise in different muscle groups

The aim of this study was to examine the effects of muscle fibre composition on muscle sympathetic nerve activity (MSNA) in response to isometric exercise. The MSNA, recorded from the tibial nerve by a microneurographic technique during contraction and following arterial occlusion, was compared in three different muscle groups: the forearm (handgrip), anterior tibialis (foot dorsal contraction), and soleus muscles (foot plantar contraction) contracted separately at intensities of 20%, 33% and 50% of the maximal voluntary force. The increases in MSNA relative to control levels during contraction and occlusion were significant at all contracting forces for handgrip and at 33% and 50% of maximal for dorsal contraction, but there were no significant changes, except during exercise at 50%, for plantar contraction. The size of the MSNA response correlated with the contraction force in all muscle groups. Pooling data for all contraction forces, there were different MSNA responses among muscle groups in contraction forces (P = 0.0001, two-way analysis of variance), and occlusion periods (P = 0.0001). The MSNA increases were in the following order of magnitude: handgrip, dorsal, and plantar contractions. The order of the fibre type composition in these three muscles is from equal numbers of types I and II fibres in the forearm to increasing number of type I fibres in the leg muscles. The different MSNA responses to the contraction of different muscle groups observed may have been due in part to muscle metaboreflex intensity influenced by their metabolic capacity which is related to by their metabolic capacity which is related to the fibre type.     

Cardiovascular responses to arm static exercise in men with thoracic spinal cord lesions

Isometric muscle contraction (static exercise) induces circulatory response. Static exercise in individuals with thoracic spinal cord injury (TSCI) induces cardiovascular response and blood redistribution to the non-exercising muscles. The aim of our study was to determine the circulatory response during arm static exercise in individuals with TSCI and able-bodied (AB) controls. Mean blood pressure (MBP), heart rate (HR), cardiac output (CO), leg skin blood flow (SBF), and leg muscle blood flow (MBF) were recorded noninvasively, total peripheral resistance (TPR) was estimated by dividing MBP by CO, and hormonal changes were measured before, during and after static 35% maximal voluntary contraction (MVC) of the arm flexor muscles in seven male individuals with TSCI (T7–T11) and seven age-comparable AB control (32.2 ± 7.6 and 31.0 ± 4.7 years, respectively). The 35% MVC was similar in TSCI and AB individuals (107.3 ± 28.2 and 101.0 ± 22.5 N, respectively). HR, CO, MBP, TPR, SBF and MBF increased in both groups during arm static exercise. Plasma epinephrine concentration increased during arm static exercise in AB controls only (P < 0.05). Circulation to leg muscles was similar in TSCI and AB individuals and the lack of sympathetic vasoconstriction in the paralyzed leg area did not alter the cardiovascular responses during 35% MVC of arm static exercise. We conclude that sympathetic vasoconstriction in the resting leg area did not contribute to the pressor reflex during 35% MVC of arm static exercise.     

Neurovascular responses to mental stress

The effects of mental stress (MS) on muscle sympathetic nerve activity (MSNA) and limb blood flows have been studied independently in the arm and leg, but they have not been studied collectively. Furthermore, the cardiovascular implications of postmental stress responses have not been thoroughly addressed. The purpose of the current investigation was to comprehensively examine concurrent neural and vascular responses during and after mental stress in both limbs. In Study 1, MSNA, blood flow (plethysmography), mean arterial pressure (MAP) and heart rate (HR) were measured in both the arm and leg in 12 healthy subjects during and after MS (5 min of mental arithmetic). MS significantly increased MAP (Δ15 ± 3 mmHg; P < 0.01) and HR (Δ19 ± 3 beats min⁻¹; P < 0.01), but did not change MSNA in the arm (14 ± 3 to 16 ± 3 bursts min⁻¹; n = 6) or leg (14 ± 2 to 15 ± 2 bursts min⁻¹; n = 8). MS decreased forearm vascular resistance (FVR) by −27 ± 7% ( P < 0.01; n = 8), while calf vascular resistance (CVR) did not change (−6 ± 5%; n = 11). FVR returned to baseline during recovery, whereas MSNA significantly increased in the arm (21 ± 3 bursts min⁻¹; P < 0.01) and leg (19 ± 3 bursts min⁻¹; P < 0.03). In Study 2, forearm and calf blood flows were measured in an additional 10 subjects using Doppler ultrasound. MS decreased FVR (−27 ± 10%; P < 0.02), but did not change CVR (5 ± 14%) as in Study 1. These findings demonstrate differential vascular control of the arm and leg during MS that is not associated with muscle sympathetic outflow. Additionally, the robust increase in MSNA during recovery may have acute and chronic cardiovascular implications.     

Effects of digoxin on muscle reflexes in normal humans

Blockade of the skeletal muscle Na⁺–K⁺-ATPase pump by digoxin could result in a more marked hyperkaliema during a forearm exercise, which in turn could stimulate the mechano- and metaboreceptors. In a randomized, double-blinded, placebo-controlled, and cross-over-design study, we measured mean blood pressure (MBP), heart rate (HR), ventilation (V _E), oxygen saturation (SpO₂), muscle sympathetic nerve activity (MSNA), venous plasma potassium and lactic acid during dynamic handgrip exercises, and local circulatory arrest in 11 healthy subjects. Digoxin enhanced MBP during exercise but not during the post-handgrip ischemia and had no effect on HR, V _E, SpO₂, and MSNA. Venous plasma potassium and lactic acid were also not affected by digoxin-induced skeletal muscle Na⁺–K⁺-ATPase blockade. We conclude that digoxin increased MBP during dynamic exercise in healthy humans, independently of changes in potassium and lactic acid. A modest direct sensitization of the muscle mechanoreceptors is unlikely and other mechanisms, independent of muscle reflexes and related to the inotropic effects of digoxin, might be implicated.     

Effects on blood pressure and autonomic nervous system function of a 12-week exercise or exercise plus DASH-diet intervention in individuals with elevated blood pressure

Aim: Hypertension is related to abnormalities in autonomic nervous system (ANS) function, with increased sympathetic output and decreased parasympathetic tone. Lifestyle interventions are the first line of treatment in hypertension, and decreased blood pressure (BP) effects may be related to changes in ANS function. Using heart rate recovery (HRR) from exercise as an index of parasympathetic tone and plasma noradrenaline as an index of sympathetic tone, we investigated the effects of lifestyle interventions on ANS function in patients with elevated BP. Methods: Sedentary participants with elevated BP were randomly assigned to either an exercise only (N = 25), exercise plus dietary approaches to stop hypertension (DASH) diet (N = 12), or waitlist control (N = 15) 12‐week intervention. Plasma noradrenaline was measured at rest and participants performed a peak exercise test before and after the intervention. HRR was calculated as peak heart rate (HR) minus HR at 1 min post‐exercise. Results: Heart rate recovery showed a significant group by time interaction; both intervention groups showed increases in HRR from pre‐ to post‐intervention, while waitlist showed no change. Similarly, both exercise plus diet and exercise groups, but not waitlist, showed significant reductions in BP from pre‐ to post‐intervention. Linear regression revealed that BP post‐intervention was significantly predicted by change in HRR when controlling for pre‐BP, age, gender and BMI. Conclusions: Lifestyle interventions induced training‐reduced BP and altered autonomic tone, indexed by HRR. This study indicates the importance of behavioural modification in hypertension and that increased parasympathetic function is associated with success in reduction of BP.