Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans

2004 ◽  
Vol 287 (5) ◽  
pp. H1944-H1949 ◽  
Author(s):  
Holly R. Middlekauff ◽  
Josephine Chiu
Keyword(s):  
Adenosine Receptors ◽  
Muscle Sympathetic Nerve Activity ◽  
Saline Control ◽  
Sympathetic Activation ◽  
Low Level ◽  
Healthy Humans ◽  
Muscle Mechanoreceptor ◽  
Rhythmic Exercise ◽  
Forearm Exercise ◽  
By Products

Evidence in healthy animals and humans is accumulating that the muscle mechanoreceptors play an important role in mediating sympathetic activation during exercise, especially rhythmic exercise. Furthermore, muscle mechanoreceptors appear to be sensitized acutely during exercise by metabolic by-products, although the identity of these by-products remains unknown. The purpose of this study was to determine whether the metabolic by-products 1) prostaglandins and/or 2) adenosine sensitize muscle mechanoreceptor control of muscle sympathetic nerve activity (MSNA) in normal humans during rhythmic exercise. MSNA was recorded using microneurography. Muscle mechanoreceptors were activated by low-level rhythmic forearm exercise for 3 min. In 16 healthy humans, intra-arterial indomethacin was infused into the exercising arm to inhibit synthesis of cyclooxygenase products. In 18 healthy humans, intra-arterial aminophylline was infused into the exercising arm to block adenosine receptors. During saline control, MSNA increased significantly during exercise. Inhibition of cycloxygenase during exercise dramatically and virtually completely eliminated the reflex sympathetic activation. Inhibition of adenosine receptors with aminophylline had no effect on the sympathetic activation during muscle mechanoreceptor stimulation. In conclusion, muscle mechanoreceptors are sensitized by cyclooxygenase products, but not by adenosine, during 3 min of low-level rhythmic handgrip exercise in healthy humans. Further studies of other metabolic by-products and of patients with enhanced muscle mechanoreceptor sensitivity, such as patients with heart failure, are warranted.

Cyclooxygenase products sensitize muscle mechanoreceptors in humans with heart failure

2008 ◽  
Vol 294 (4) ◽  
pp. H1956-H1962 ◽  
Author(s):  
Holly R. Middlekauff ◽  
Josephine Chiu ◽  
Michele A. Hamilton ◽  
Gregg C. Fonarow ◽  
W. Robb MacLellan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Muscle Sympathetic Nerve Activity ◽  
Saline Control ◽  
Mechanical Stimuli ◽  
Early Generation ◽  
Low Level ◽  
Endogenous Adenosine ◽  
Healthy Humans ◽  
Muscle Mechanoreceptor ◽  
By Products

Prior work in animals and humans suggests that muscle mechanoreceptor control of sympathetic activation [muscle sympathetic nerve activity (MSNA)] during exercise in heart failure (HF) patients is heightened compared with that of healthy humans and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether cyclooxygenase products and/or endogenous adenosine, two metabolites of ischemic exercise, sensitize muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in HF patients. Indomethacin, which inhibits the production of prostaglandins, and saline control were infused in 12 HF patients. In a different protocol, aminophylline, which inhibits adenosine receptors, and saline control were infused in 12 different HF patients. MSNA was recorded (microneurography). During exercise following saline, MSNA increased in the first minute of exercise, consistent with baseline heightened mechanoreceptor sensitivity. MSNA continued to increase during 3 min of RHG, indicative that muscle mechanoreceptors are sensitized by ischemia metabolites. Indomethacin, but not aminophylline, markedly attenuated the increase in MSNA during the entire 3 min of low-level rhythmic exercise, consistent with the sensitization of muscle mechanoreceptors by cyclooxygenase products. Interestingly, even the early increase in MSNA was abolished by indomethacin infusion, indicative of the very early generation of cyclooxygenase products after the onset of exercise in HF patients. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in HF. Cyclooxygenase products, but not endogenous adenosine, play a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli, which also appears to be mediated by the early generation of cyclooxygenase products, resulting in exaggerated early increases in MSNA.

Muscle mechanoreceptor sensitivity in heart failure

2004 ◽  
Vol 287 (5) ◽  
pp. H1937-H1943 ◽  
Author(s):  
Holly R. Middlekauff ◽  
Josephine Chiu ◽  
Michele A. Hamilton ◽  
Gregg C. Fonarow ◽  
W. Robb MacLellan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Lactic Acid ◽  
Circulatory Arrest ◽  
Saline Control ◽  
Mechanical Stimuli ◽  
Exercise Protocol ◽  
Passive Exercise ◽  
Healthy Humans ◽  
Muscle Mechanoreceptor ◽  
By Products

Prior work in animals suggests that muscle mechanoreceptor control of sympathetic activation (MSNA) during exercise in heart failure (HF) is heightened and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether 1) muscle mechanoreceptor control of MSNA is enhanced in HF patients and 2) lactic acid sensitizes muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in healthy humans and patients with HF. Dichloroacetate (DCA), which reduces the production of lactic acid, or saline control was infused in 12 patients with HF and 13 controls during RHG. MSNA was recorded (microneurography). After saline was administered and during exercise thereafter, MSNA increased earlier in HF compared with controls, consistent with baseline-heightened mechanoreceptor sensitivity. In both HF and controls, MSNA increased during the 3-min exercise protocol, consistent with further sensitization of muscle mechanoreceptors by metabolic by-product(s). During posthandgrip circulatory arrest, MSNA returned rapidly to baseline levels, excluding the muscle metaboreceptors as mediators of the sympathetic excitation during RHG. To isolate muscle mechanoreceptors from central command, we utilized passive exercise in 8 HF and 11 controls, and MSNA was recorded. MSNA increased significantly during passive exercise in HF but not in controls. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in healthy humans, and this muscle mechanoreceptor control is augmented further in HF. Neither lactate generation nor the fall in pH during RHG plays a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli resulting in exaggerated early increases in MSNA.

scholarly journals Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity

2010 ◽  
Vol 299 (3) ◽  
pp. H925-H931 ◽  
Author(s):  
G. S. Gilmartin ◽  
M. Lynch ◽  
R. Tamisier ◽  
J. W. Weiss
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Intermittent Hypoxia ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Chronic Intermittent Hypoxia ◽  
Sympathetic Activation ◽  
Nerve Activity ◽  
Blood Pressure Elevation ◽  
Healthy Humans

Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17–24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr ( n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 ± 1.3 vs. 74 ± 1.7 mmHg, P < 0.01), MSNA [9.94 ± 2.0 to 14.63 ± 1.5 bursts/min ( P < 0.05); 16.89 ± 3.2 to 26.97 ± 3.3 bursts/100 heartbeats (hb) ( P = 0.01)], and forearm vascular resistance (FVR) (35.3 ± 5.8 vs. 55.3 ± 6.5 mmHg·ml−1·min·100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR.

Forearm elevation augments sympathetic activation during handgrip exercise in humans

2002 ◽  
Vol 103 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Daisaku MICHIKAMI ◽  
Atsunori KAMIYA ◽  
Qi FU ◽  
Yuki NIIMI ◽  
Satoshi IWASE ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Muscle Sympathetic Nerve Activity ◽  
Voluntary Contraction ◽  
Sympathetic Activation ◽  
Handgrip Exercise ◽  
Excitatory Effect ◽  
Muscle Metaboreflex ◽  
Forearm Exercise ◽  
Exercise In Humans

Although angina pectoris in patients with coronary heart disease often occurs when their forearms are in an elevated position for a prolonged period, and sympathetic activation is a major cause of this condition, little is known about the physiological effects of forearm elevation on sympathetic activity during forearm exercise. We hypothesized that forearm elevation augments sympathetic activation during the static handgrip exercise in humans. A total of 10 healthy male volunteers performed 2min of static handgrip exercise at 30% of maximal voluntary contraction followed by 2min of post-exercise muscle ischaemia (PEMI; specific activation of the muscle metaboreflex) with two forearm positions: the exercising forearm was elevated 50cm above the heart (forearm-elevated trial) or fixed at the level of the heart (heart-level trial). Muscle sympathetic nerve activity (MSNA), blood pressure and heart rate were monitored. MSNA increased during handgrip exercise in both forearm positions (P<0.001); the increase was 51% greater in the forearm-elevated trial (516±99 arbitrary units) than in the heart-level trial (346±44units; P<0.05). The increase in mean blood pressure was 8.4mmHg greater during exercise in the forearm-elevated trial (P<0.05), while changes in heart rate were similar in both forearm positions. The increase in MSNA during PEMI was 71% greater in the forearm-elevated trial (393±71 arbitrary units/min) than in the heart-level trial (229±29units/min; P<0.05). These results support the hypothesis that forearm elevation augments sympathetic activation during handgrip exercise. The excitatory effect of forearm elevation on exercising MSNA may be mediated primarily by increased activation of the muscle metaboreflex.

scholarly journals Neurocirculatory consequences of intermittent asphyxia in humans

2000 ◽  
Vol 89 (4) ◽  
pp. 1333-1339 ◽  
Author(s):  
Ailiang Xie ◽  
James B. Skatrud ◽  
David C. Crabtree ◽  
Dominic S. Puleo ◽  
Brian M. Goodman ◽  
...  
Keyword(s):  
Muscle Sympathetic Nerve Activity ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Sleep Apnea Syndrome ◽  
Sympathetic Activation ◽  
Air Breathing ◽  
Healthy Humans ◽  
Short Term Exposure ◽  
Chemical Stimuli ◽  
End Tidal

We examined the neurocirculatory and ventilatory responses to intermittent asphyxia (arterial O2 saturation = 79–85%, end-tidal Pco 2 =3–5 Torr above eupnea) in seven healthy humans during wakefulness. The intermittent asphyxia intervention consisted of 20-s asphyxic exposures alternating with 40-s periods of room-air breathing for a total of 20 min. Minute ventilation increased during the intermittent asphyxia period (14.2 ± 2.0 l/min in the final 5 min of asphyxia vs. 7.5 ± 0.4 l/min in baseline) but returned to the baseline level within 2 min after completion of the series of asphyxic exposures. Muscle sympathetic nerve activity increased progressively, reaching 175 ± 12% of baseline in the final 5 min of the intervention. Unlike ventilation, sympathetic activity remained elevated for at least 20 min after removal of the chemical stimuli (150 ± 10% of baseline in the last 5 min of the recovery period). Intermittent asphyxia caused a small, but statistically significant, increase in heart rate (64 ± 4 beats/min in the final 5 min of asphyxia vs. 61 ± 4 beats/min in baseline); however, this increase was not sustained after the return to room-air breathing. These data demonstrate that relatively short-term exposure to intermittent asphyxia causes sympathetic activation that persists after removal of the chemical stimuli. This carryover effect provides a potential mechanism whereby intermittent asphyxia during sleep could lead to chronic sympathetic activation in patients with sleep apnea syndrome.

Short-term intermittent hypoxia enhances sympathetic responses to continuous hypoxia in humans

2007 ◽  
Vol 103 (3) ◽  
pp. 835-842 ◽  
Author(s):  
Urs A. Leuenberger ◽  
Cynthia S. Hogeman ◽  
Sadeq Quraishi ◽  
Latoya Linton-Frazier ◽  
Kristen S. Gray
Keyword(s):  
Blood Pressure ◽  
Sleep Apnea ◽  
Sympathetic Activity ◽  
Intermittent Hypoxia ◽  
Muscle Sympathetic Nerve Activity ◽  
Acute Hypoxia ◽  
Short Term ◽  
Healthy Humans ◽  
Obstructive Sleep ◽  
Normal Humans

Short-term intermittent hypoxia leads to sustained sympathetic activation and a small increase in blood pressure in healthy humans. Because obstructive sleep apnea, a condition associated with intermittent hypoxia, is accompanied by elevated sympathetic activity and enhanced sympathetic chemoreflex responses to acute hypoxia, we sought to determine whether intermittent hypoxia also enhances chemoreflex activity in healthy humans. To this end, we measured the responses of muscle sympathetic nerve activity (MSNA, peroneal microneurography) to arterial chemoreflex stimulation and deactivation before and following exposure to a paradigm of repetitive hypoxic apnea (20 s/min for 30 min; O2 saturation nadir 81.4 ± 0.9%). Compared with baseline, repetitive hypoxic apnea increased MSNA from 113 ± 11 to 159 ± 21 units/min ( P = 0.001) and mean blood pressure from 92.1 ± 2.9 to 95.5 ± 2.9 mmHg ( P = 0.01; n = 19). Furthermore, compared with before, following intermittent hypoxia the MSNA (units/min) responses to acute hypoxia [fraction of inspired O2 (FiO2) 0.1, for 5 min] were enhanced (pre- vs. post-intermittent hypoxia: +16 ± 4 vs. +49 ± 10%; P = 0.02; n = 11), whereas the responses to hyperoxia (FiO2 0.5, for 5 min) were not changed significantly ( P = NS; n = 8). Thus 30 min of intermittent hypoxia is capable of increasing sympathetic activity and sensitizing the sympathetic reflex responses to hypoxia in normal humans. Enhanced sympathetic chemoreflex activity induced by intermittent hypoxia may contribute to altered neurocirculatory control and adverse cardiovascular consequences in sleep apnea.

scholarly journals Sympathetic activation by lower body negative pressure decreases kidney perfusion without inducing hypoxia in healthy humans

2018 ◽  
Vol 30 (2) ◽  
pp. 149-156 ◽  
Author(s):  
René van der Bel ◽  
Jasper Verbree ◽  
Oliver J. Gurney-Champion ◽  
Matthias J. P. van Osch ◽  
Erik S. G. Stroes ◽  
...  
Keyword(s):  
Negative Pressure ◽  
Lower Body Negative Pressure ◽  
Lower Body ◽  
Sympathetic Activation ◽  
Healthy Humans ◽  
Kidney Perfusion

The impact of 6 months of exercise-based cardiac rehabilitation on sympathetic neural recruitment during apneic stress

2021 ◽  
Author(s):  
Andrew D'Souza ◽  
Mark B. Badrov ◽  
Katelyn N. Wood ◽  
Sophie Lalande ◽  
Neville Gordon Suskin ◽  
...  
Keyword(s):  
Cardiac Rehabilitation ◽  
Sympathetic Activity ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Firing Frequency ◽  
Sympathetic Activation ◽  
Nerve Activity ◽  
Sympathetic Nervous ◽  
Discharge Patterns ◽  
The Impact

The current study evaluated the hypothesis that six months of exercise-based cardiac rehabilitation (CR) would improve sympathetic neural recruitment in patients with ischemic heart disease (IHD). Microneurography was used to evaluate action potential (AP) discharge patterns within bursts of muscle sympathetic nerve activity (MSNA), in eleven patients with IHD (1 female; 61±9 years) pre- (Pre-CR) and post- six months of aerobic and resistance training-based CR (Post-CR). Measures were made at baseline and during maximal voluntary end-inspiratory (EI-APN) and end-expiratory apneas (EE-APN). Data were analyzed during 1-minute of baseline and the second half of apneas. At baseline, overall sympathetic activity was less Post-CR (all P<0.01). During EI-APN, AP recruitment was not observed Pre-CR (all P>0.05) but increases in both within-burst AP firing frequency (∆Pre-CR: 2±3 AP spikes/burst vs. ∆Post-CR: 4±3 AP spikes/burst; P=0.02) and AP cluster recruitment (∆Pre-CR: -1±2 vs. ∆Post-CR: 2±2; P<0.01) were observed in Post-CR tests. In contrast, during EE-APN, AP firing frequency was not different Post-CR compared to Pre-CR tests (∆Pre-CR: 269±202 spikes/min vs. ∆Post-CR: 232±225 spikes/min; P=0.54), and CR did not modify the recruitment of new AP clusters (∆Pre-CR: -1±3 vs. ∆Post-CR: 0±1; P=0.39), or within-burst firing frequency (∆Pre-CR: 3±3 AP spikes/burst vs. ∆Post-CR: 2±2 AP spikes/burst; P=0.21). These data indicate that CR improves some of the sympathetic nervous system dysregulation associated with cardiovascular disease, primarily via a reduction in resting sympathetic activation. However, the benefits of CR on sympathetic neural recruitment may depend upon the magnitude of initial impairment.

Neurocirculatory consequences of abrupt change in sleep state in humans

1996 ◽  
Vol 80 (5) ◽  
pp. 1627-1636 ◽  
Author(s):  
B. J. Morgan ◽  
D. C. Crabtree ◽  
D. S. Puleo ◽  
M. S. Badr ◽  
F. Toiber ◽  
...  
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Muscle Sympathetic Nerve Activity ◽  
Intrathoracic Pressure ◽  
Nrem Sleep ◽  
Auditory Stimuli ◽  
Sleep State ◽  
Healthy Humans ◽  
Pressor Responses

The arterial pressure elevations that accompany sleep apneas may be caused by chemoreflex stimulation, negative intrathoracic pressure, and/or arousal. To assess the neurocirculatory effects of arousal alone, we applied graded auditory stimuli during non-rapid-eye-movement (NREM) sleep in eight healthy humans. We measured muscle sympathetic nerve activity (intraneural microelectrodes), electroencephalogram (EEG; C4/A1 and O1/A2), arterial pressure (photoelectric plethysmography), heart rate (electrocardiogram), and stroke volume (impedance cardiography). Auditory stimuli caused abrupt increases in systolic and diastolic pressures (21 +/- 2 and 15 +/- 1 mmHg) and heart rate (11 +/- 2 beats/min). Cardiac output decreased (-10%). Stimuli that produced EEG evidence of arousal evoked one to two large bursts of sympathetic activity (316 +/- 46% of baseline amplitude). Stimuli that did not alter EEG frequency produced smaller but consistent pressor responses even though no sympathetic activation was observed. We conclude that arousal from NREM sleep evokes a pressor response caused by increased peripheral vascular resistance. Increased sympathetic outflow to skeletal muscle may contribute to, but is not required for, this vasoconstriction. The neurocirculatory effects of arousal may augment those caused by asphyxia during episodes of sleep-disordered breathing.

Sign in / Sign up

Export Citation Format

Share Document