Muscle stiffening is associated with muscle mechanoreflex-mediated cardioacceleration

Abstract Purpose The exercise pressor reflex (EPR) plays a fundamental role in physiological reactions to exercise in humans and in the pathophysiology of cardiovascular disorders. There is no “gold standard” method for EPR assessment; therefore, we propose a new protocol for testing interactions between the muscle mechanoreflex and metaboreflex (major components of EPR). Methods Thirty-four healthy subjects (mean age [± standard deviation] 24 ± 4 years, 22 men) were enrolled in the study. During the study, the hemodynamic and ventilatory parameters of these subjects were continuously monitored using our proposed assessment method. This assessment method consists of an initial 5-min rest period (baseline) followed by 5 min of passive cycling (PC) on an automated cycle ergometer (mechanoreceptor stimulation), after which tourniquet cuffs located bilaterally on the upper thighs are inflated for 3 min to evoke venous and arterial regional circulatory occlusion (CO) during PC (metaboreceptor stimulation). Deflation of the tourniquet cuffs is followed by a second 5 min of PC and finally by a 5-min recovery time. The control test comprises a 5-min rest period, followed by 3 min of CO only and a final 5-min recovery. Results Mean arterial pressure (MAP) and minute ventilation (MV) increased significantly during PC (MAP: from 90 ± 9.3 to 95 ± 9.7 mmHg; MV: from 11.5 ± 2.5 to 13.5 ± 2.9 L/min; both p < 0.05) and again when CO was applied (MAP: from 95 ± 9.7 to 101 ± 11.0 mmHg; MV: from 13.5 ± 2.9 to 14.8 ± 3.8 L/min; both p < 0.05). In the control test there was a slight increase in MAP during CO (from 92 ± 10.5 to 94 ± 10.0 mmHg; p < 0.05) and no changes in the ventilatory parameters. Conclusion Bilateral leg passive cycling with concomitant circulatory occlusion is a new, simple and effective method for testing interactions between the mechanoreflex and metaboreflex in humans.

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P2 antagonist PPADS attenuates responses of thin fiber afferents to static contraction and tendon stretch

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01051.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. H1214-H1219 ◽

Cited By ~ 27

Author(s):

Angela E. Kindig ◽

Shawn G. Hayes ◽

Ramy L. Hanna ◽

Marc P. Kaufman

Keyword(s):

Pyridoxal Phosphate ◽

Discharge Rate ◽

Muscle Afferents ◽

Group Iv ◽

Disulfonic Acid ◽

Group Iii ◽

Exercise Pressor Reflex ◽

Pressor Responses ◽

Static Contraction ◽

Muscle Mechanoreflex

Injection into the arterial supply of skeletal muscle of pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a P2 receptor antagonist, has been shown previously to attenuate the reflex pressor responses to both static contraction and to tendon stretch. In decerebrated cats, we tested the hypothesis that PPADS attenuated the responses of groups III and IV muscle afferents to static contraction as well as to tendon stretch. We found that injection of PPADS (10 mg/kg) into the popliteal artery attenuated the responses of both group III ( n = 16 cats) and group IV afferents ( n = 14 cats) to static contraction. Specifically, static contraction before PPADS injection increased the discharge rate of the group III afferents from 0.1 ± 0.05 to 1.6 ± 0.5 impulses/s, whereas contraction after PPADS injection increased the discharge of the group III afferents from 0.2 ± 0.1 to only 1.0 ± 0.5 impulses/s ( P < 0.05). Likewise, static contraction before PPADS injection increased the discharge rate of the group IV afferents from 0.3 ± 0.1 to 1.0 ± 0.3 impulses/s, whereas contraction after PPADS injection increased the discharge of the group IV afferents from 0.2 ± 0.1 to only 0.3 ± 0.1 impulses/s ( P < 0.05). In addition, PPADS significantly attenuated the responses of group III afferents to tendon stretch but had no effect on the responses of group IV afferents. Our findings suggest that both groups III and IV afferents are responsible for evoking the purinergic component of the exercise pressor reflex, whereas only group III afferents are responsible for evoking the purinergic component of the muscle mechanoreflex that is evoked by tendon stretch.

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Muscle mechanoreflex activation via passive calf stretch causes renal vasoconstriction in healthy humans

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00322.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. R956-R964 ◽

Cited By ~ 13

Author(s):

Rachel C. Drew ◽

Cheryl A. Blaha ◽

Michael D. Herr ◽

Ruda Cui ◽

Lawrence I. Sinoway

Keyword(s):

Voluntary Contraction ◽

Lower Limbs ◽

Renal Vasoconstriction ◽

Healthy Humans ◽

Arterial Blood ◽

Vasoconstrictor Response ◽

Muscle Mechanoreflex ◽

Metabolite Accumulation ◽

Young Subjects ◽

Renal Vascular

Reflex renal vasoconstriction occurs during exercise, and renal vasoconstriction in response to upper-limb muscle mechanoreflex activation has been documented. However, the renal vasoconstrictor response to muscle mechanoreflex activation originating from lower limbs, with and without local metabolite accumulation, has not been assessed. Eleven healthy young subjects (26 ± 1 yr; 5 men) underwent two trials involving 3-min passive calf muscle stretch (mechanoreflex) during 7.5-min lower-limb circulatory occlusion (CO). In one trial, 1.5-min 70% maximal voluntary contraction isometric calf exercise preceded CO to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex; 70% trial). A control trial involved no exercise before CO (mechanoreflex alone; 0% trial). Beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), mean arterial blood pressure (MAP; photoplethysmographic finger cuff), and heart rate (electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as MAP/RBFV. All baseline cardiovascular variables were similar between trials. Stretch increased RVR and decreased RBFV in both trials (change from CO with stretch: RVR – 0% trial = Δ 10 ± 2%, 70% trial = Δ 7 ± 3%; RBFV – 0% trial = Δ −3.8 ± 1.1 cm/s, 70% trial = Δ −2.7 ± 1.5 cm/s; P < 0.05 for RVR and RBFV). These stretch-induced changes were of similar magnitudes in both trials, e.g., with and without local metabolite accumulation, as well as when thromboxane production was inhibited. These findings suggest that muscle mechanoreflex activation via passive calf stretch causes renal vasoconstriction, with and without muscle metaboreflex activation, in healthy humans.

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Metabolic acidosis augments exercise pressor responses in chronic kidney disease

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00076.2019 ◽

2019 ◽

Vol 317 (2) ◽

pp. R312-R318

Author(s):

Justin D. Sprick ◽

Doree Lynn Morison ◽

Ida T. Fonkoue ◽

Yunxiao Li ◽

Dana DaCosta ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Near Infrared ◽

Voluntary Contraction ◽

Normal Serum ◽

Serum Bicarbonate ◽

Pressor Responses ◽

Increased Risk ◽

Muscle Mechanoreflex

Chronic kidney disease (CKD) patients experience augmented blood pressure (BP) reactivity during exercise that is associated with an increased risk of cardiovascular mortality. Exaggerated exercise pressor responses in CKD are in part mediated by augmented sympathetic nerve activation due to heightened muscle mechanoreflex. One mechanism that may lead to sensitization of the muscle mechanoreflex in CKD is metabolic acidosis. We hypothesized that CKD patients with low serum [bicarbonate] would exhibit exaggerated increases in arterial BP, greater reductions in muscle interstitial pH, and fatigue earlier during exercise compared with CKD patients with normal serum bicarbonate concentration ([bicarbonate]). Eighteen CKD participants with normal serum [bicarbonate] (≥24 mmol/l, normal-bicarb) and 9 CKD participants with mild metabolic acidosis ([bicarbonate] range 20–22 mmol/l, low-bicarb) performed rhythmic handgrip (RHG) exercise to volitional fatigue at 40% of maximal voluntary contraction. BP, heart rate, and muscle interstitial pH using near infrared spectroscopy were measured continuously. While mean arterial pressure (MAP) increased with exercise in both groups ( P ≤ 0.002), CKD with low-bicarb had an exaggerated MAP response compared with CKD with normal-bicarb (+5.9 ± 1.3 mmHg/30 s vs. +2.6 ± 0.5 mmHg/30 s, P = 0.01). The low-bicarb group reached exhaustion earlier than the normal-bicarb group (179 ± 21 vs. 279 ± 19 s, P = 0.003). There were no differences in the change in muscle interstitial pH during exercise between groups ( P = 0.31). CKD patients with metabolic acidosis have augmented exercise-induced increases in BP and poorer exercise tolerance. There was no difference in change in muscle interstitial pH between groups, however, suggesting that augmented exercise BP responses in metabolic acidosis are not due to impaired muscle-buffering capacity.

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Aspirin augments carotid-cardiac baroreflex sensitivity during muscle mechanoreflex and metaboreflex activation in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00100.2013 ◽

2013 ◽

Vol 115 (8) ◽

pp. 1183-1190 ◽

Cited By ~ 6

Author(s):

Rachel C. Drew ◽

Matthew D. Muller ◽

Cheryl A. Blaha ◽

Jessica L. Mast ◽

Michael D. Herr ◽

...

Keyword(s):

Low Dose ◽

Voluntary Contraction ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Prostaglandin F ◽

Increased Sensitivity ◽

Muscle Mechanoreflex ◽

Metabolite Accumulation ◽

Young Subjects ◽

Maximal Gain

Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to −80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% ( P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; −0.71 ± 0.14 vs. −0.37 ± 0.08 and GOP; −0.69 ± 0.13 vs. −0.35 ± 0.12 beats·min-1·mmHg−1 for aspirin and placebo, respectively; P < 0.05). CBR-HR function curves were reset similarly with aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors.

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A Role for Brainstem Nitric Oxide in the Development of Muscle Mechanoreflex Overactivity in Hypertension

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000323229.19307.b7 ◽

2008 ◽

Vol 40 (Supplement) ◽

pp. S318

Author(s):

Anna K. Leal ◽

Jere H. Mitchell ◽

Scott A. Smith

Keyword(s):

Nitric Oxide ◽

Muscle Mechanoreflex

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Hyperadditive ventilatory response arising from interaction between the carotid chemoreflex and the muscle mechanoreflex in healthy humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00009.2018 ◽

2018 ◽

Vol 125 (1) ◽

pp. 215-225 ◽

Cited By ~ 10

Author(s):

Talita M. Silva ◽

Liliane C. Aranda ◽

Marcelle Paula-Ribeiro ◽

Diogo M. Oliveira ◽

Wladimir M. Medeiros ◽

...

Keyword(s):

Ventilatory Response ◽

Passive Movement ◽

Breathing Frequency ◽

Low Intensity ◽

Healthy Humans ◽

Knee Movement ◽

Neural Interactions ◽

Muscle Mechanoreflex ◽

Low Intensity Exercise ◽

Stimulation Of

Physical exercise potentiates the carotid chemoreflex control of ventilation (VE). Hyperadditive neural interactions may partially mediate the potentiation. However, some neural interactions remain incompletely explored. As the potentiation occurs even during low-intensity exercise, we tested the hypothesis that the carotid chemoreflex and the muscle mechanoreflex could interact in a hyperadditive fashion. Fourteen young healthy subjects inhaled randomly, in separate visits, 12% O2 to stimulate the carotid chemoreflex and 21% O2 as control. A rebreathing circuit maintained isocapnia. During gases administration, subjects either remained at rest (i.e., normoxic and hypoxic rest) or the muscle mechanoreflex was stimulated via passive knee movement (i.e., normoxic and hypoxic movement). Surface muscle electrical activity did not increase during the passive movement, confirming the absence of active contractions. Hypoxic rest and normoxic movement similarly increased VE [change (mean ± SE) = 1.24 ± 0.72 vs. 0.73 ± 0.43 l/min, respectively; P = 0.46], but hypoxic rest only increased tidal volume (Vt), and normoxic movement only increased breathing frequency (BF). Hypoxic movement induced greater VE and mean inspiratory flow (Vt/Ti) increase than the sum of hypoxic rest and normoxic movement isolated responses (VE change: hypoxic movement = 3.72 ± 0.81 l/min vs. sum = 1.96 ± 0.83 l/min, P = 0.01; Vt/Ti change: hypoxic movement = 0.13 ± 0.03 l/s vs. sum = 0.06 ± 0.03 l/s, P = 0.02). Moreover, hypoxic movement increased both Vt and BF. Collectively, the results indicate that the carotid chemoreflex and the muscle mechanoreflex interacted, mediating a hyperadditive ventilatory response in healthy humans. NEW & NOTEWORTHY The main finding of this study was that concomitant carotid chemoreflex and muscle mechanoreflex stimulation provoked greater ventilation increase than the sum of ventilation increase induced by stimulation of each reflex in isolation, which, consequently, supports that the carotid chemoreflex and the muscle mechanoreflex interacted, mediating a hyperadditive ventilatory response in healthy humans.

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