scholarly journals Role played by acid-sensitive ion channels in evoking the exercise pressor reflex

2008 ◽  
Vol 295 (4) ◽  
pp. H1720-H1725 ◽  
Author(s):  
Shawn G. Hayes ◽  
Jennifer L. McCord ◽  
Jon Rainier ◽  
Zhuqing Liu ◽  
Marc P. Kaufman
Keyword(s):  
Lactic Acid ◽  
Ion Channels ◽  
Sodium Channels ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
Pressor Responses ◽  
Pressor Reflex

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half ( P < 0.05) the pressor responses to both contraction and to lactic acid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.

scholarly journals The magnitude of the exercise pressor reflex is influenced by the active skeletal muscle mass in the decerebrate rat

2020 ◽  
Vol 318 (1) ◽  
pp. R30-R37
Author(s):  
Juan A. Estrada ◽  
Guillaume P. Ducrocq ◽  
Marc P. Kaufman
Keyword(s):  
Lactic Acid ◽  
Muscle Mass ◽  
Calcaneal Tendon ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
Hindlimb Muscles ◽  
Pressor Responses ◽  
Decerebrate Rat ◽  
Pressor Reflex ◽  
Stimulation Of

The exercise pressor reflex is composed of two components, namely the muscle mechanoreflex and the muscle metaboreflex. The afferents evoking the two components are either thinly myelinated (group III) or unmyelinated (group IV); in combination they are termed “thin fiber afferents.” The exercise pressor reflex is often studied in unanesthetized, decerebrate rats. However, the relationship between the magnitude of this reflex and the number of thin fiber afferents stimulated by muscle contraction is unknown. This lack of knowledge prompted us to test the hypothesis that the magnitude of the exercise pressor reflex was directly proportional to the amount of muscle mass activated. Muscle mechanoreceptors were stimulated by stretching the calcaneal tendon. Likewise, muscle metaboreceptors were stimulated by injecting lactic acid into the arterial supply of the hindlimb muscles. In addition, both muscle mechanoreceptors and metaboreceptors were stimulated by statically contracting the hindlimb muscles. We found that simultaneous bilateral (both hindlimbs) stimulation of thin fiber afferents with stretch, lactic acid, and static contraction evoked significantly greater pressor responses than did unilateral (one hindlimb) stimulation of these afferents. In addition, the magnitude of the pressor responses to bilateral simultaneous stimulation of thin fiber afferents evoked by stretch, lactic acid, and contraction was not significantly different from the magnitude of the sum of the pressor responses evoked by unilateral stimulation of these afferents by stretch, lactic acid, and contraction. We conclude that the magnitude of the exercise pressor reflex and its two components is dependent on the number of afferents stimulated.

scholarly journals Effect of knockout of the ASIC3 on cardiovascular reflexes arising from hindlimb muscle in decerebrated rats

2019 ◽  
Vol 317 (5) ◽  
pp. R641-R648 ◽  
Author(s):  
Joyce S. Kim ◽  
Jonathan E. Harms ◽  
Victor Ruiz-Velasco ◽  
Marc P. Kaufman
Keyword(s):  
Lactic Acid ◽  
Muscle Afferents ◽  
Cardiovascular Reflexes ◽  
Calcaneal Tendon ◽  
Group Iii ◽  
Exercise Pressor Reflex ◽  
Arterial Blood ◽  
Pressor Responses ◽  
Alternative Approach ◽  
Pressor Reflex

The exercise pressor reflex is initiated by the contraction-induced activation of group III and IV muscle afferents. The reflex is manifested by increases in arterial blood pressure and cardiac output, which, in turn, are generated by increases in the sympathetic outflow to the heart and vasculature and decreases in the vagal outflow to the heart. In previous experiments, we used a pharmacological approach to assess the role played by the acid-sensing ion channel 3 (ASIC3) on group III and IV afferents in evoking the exercise pressor reflex. In the present experiments, we used an alternative approach, namely functional knockout (KO) of the ASIC3 gene, to confirm and extend our previous finding that pharmacological blockade of the ASIC3 had only a small impact on the expression of the exercise pressor reflex when the arterial supply to the contracting hindlimb muscles of rats was patent. Using this alternative approach, we compared the magnitude of the exercise pressor reflex evoked in ASIC3 KO rats with that evoked in their wild-type (WT) counterparts. We found both WT and ASIC3 KO rats displayed similar pressor responses to static contraction (WT, n = 10, +12 ± 2 mmHg; KO, n = 9, +11 ± 2 mmHg) and calcaneal tendon stretch (WT, n = 9, +13 ± 2 mmHg; KO, n = 7, +11 ± 2 mmHg). Likewise, both WT and ASIC3 KO displayed similar pressor responses to intra-arterial injection of 12 mM lactic acid (WT, n = 9, +14 ± 3 mmHg; KO, n = 8, +18 ± 5 mmHg), 24 mM lactic acid (WT, n = 9,+24 ± 2 mmHg; KO, n = 8, +20 ± 5 mmHg), capsaicin (WT, n = 9,+27 ± 5 mmHg; KO, n = 10, +29 ± 5 mmHg), and diprotonated phosphate ([Formula: see text]; WT, n = 6,+22 ± 3 mmHg; KO, n = 6, +32 ± 6 mmHg). We conclude that redundant receptors are responsible for evoking the pressor reflexes arising from group III and IV afferents.

scholarly journals Acid-sensing ion channels contribute to the metaboreceptor component of the exercise pressor reflex

2009 ◽  
Vol 297 (1) ◽  
pp. H443-H449 ◽  
Author(s):  
Jennifer L. McCord ◽  
Hirotsugu Tsuchimochi ◽  
Marc P. Kaufman
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Pressor Response ◽  
Triceps Surae ◽  
Exercise Pressor Reflex ◽  
Acid Sensing Ion Channels ◽  
Pressor Responses ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Triceps Surae Muscles

The exercise pressor reflex is evoked by both mechanical and metabolic stimuli arising in contracting skeletal muscle. Recently, the blockade of acid-sensing ion channels (ASICs) with amiloride and A-316567 attenuated the reflex. Moreover, amiloride had no effect on the mechanoreceptor component of the reflex, prompting us to determine whether ASICs contributed to the metaboreceptor component of the exercise pressor reflex. The metaboreceptor component can be assessed by measuring mean arterial pressure during postcontraction circulatory occlusion when only the metaboreceptors are stimulated. We examined the effects of amiloride (0.5 μg/kg), A-317567 (10 mM, 0.5 ml), and saline (0.5 ml) on the pressor response to and after static contraction while the circulation was occluded in 30 decerebrated cats. Amiloride ( n = 11) and A-317567 ( n = 7), injected into the arterial supply of the triceps surae muscles, attenuated the pressor responses both to contraction while the circulation was occluded and to postcontraction circulatory occlusion (all, P < 0.05). Saline ( n = 11), however, had no effect on the pressor responses to contraction while the circulation was occluded or to postcontraction circulatory occlusion (both, P > 0.79). Our findings led us to conclude that ASICs contribute to the metaboreceptor component of the exercise pressor reflex.

scholarly journals ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex in rats

2020 ◽  
Vol 318 (1) ◽  
pp. H78-H89 ◽  
Author(s):  
Guillaume P. Ducrocq ◽  
Joyce S. Kim ◽  
Juan A. Estrada ◽  
Marc P. Kaufman
Keyword(s):  
Lactic Acid ◽  
Ion Channel ◽  
Pressor Response ◽  
Triceps Surae ◽  
Exercise Pressor Reflex ◽  
Metabolic Component ◽  
Pressor Responses ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Triceps Surae Muscles

The role of the acid-sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex is unknown, despite the fact that ASIC1a is opened by decreases in pH in the physiological range. This fact prompted us to test the hypothesis that ASIC1a plays an important role in evoking the exercise pressor reflex in decerebrated rats with freely perfused hindlimb muscles. To test this hypothesis, we measured the effect of injecting two ASIC1a blockers into the arterial supply of the triceps surae muscles on the reflex pressor responses to four maneuvers, namely 1) static contraction of the triceps surae muscles (i.e., the exercise pressor reflex), 2) calcaneal tendon stretch, 3) intra-arterial injection of lactic acid, and 4) intra-arterial injection of diprotonated phosphate. We found that the 2 ASIC1a blockers, psalmotoxin-1 (200 ng/kg) and mambalgin-1 (6.5 μg/kg), decreased the pressor responses to static contraction as well as the peak pressor responses to injection of lactic acid and diprotonated phosphate. In contrast, neither ASIC1a blocker had any effect on the pressor responses to tendon stretch. Importantly, we found that ASIC1a blockade significantly decreased the pressor response to static contraction after a latency of at least 8 s. Our results support the hypothesis that ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex. NEW & NOTEWORTHY The role played by acid-sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex remains unknown. In decerebrated rats with freely perfused femoral arteries, blocking ASIC1a with psalmotoxin-1 or mambalgin-1 significantly attenuated the pressor response to static contraction, lactic acid, and diprotonated phosphate injection but had no effect on the pressor response to stretch. We conclude that ASIC1a plays a key role in evoking the exercise pressor reflex by responding to contraction-induced metabolites, such as protons.

High concentrations of 17β-estradiol attenuate the exercise pressor reflex in male cats

2003 ◽  
Vol 94 (4) ◽  
pp. 1431-1436 ◽  
Author(s):  
Petra M. Schmitt ◽  
Marc P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Muscle Afferents ◽  
Central Command ◽  
Physiological Level ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
17Β Estradiol ◽  
Pressor Reflex ◽  
High Concentrations ◽  
Decerebrate Cats

Previously, intravenous injection of 17β-estradiol in decerebrate male cats was found to attenuate central command but not the exercise pressor reflex. This latter finding was surprising because the dorsal horn, the spinal site receiving synaptic input from thin-fiber muscle afferents, is known to contain estrogen receptors. We were prompted, therefore, to reexamine this issue. Instead of injecting 17β-estradiol intravenously, we applied it topically to the L7 and S1 spinal cord of male decerebrate cats. We found that topical application (150–200 μl) of 17β-estradiol in concentrations of 0.01, 0.1, and 1 μg/ml had no effect on the exercise pressor reflex, whereas a concentration of 10 μg/ml attenuated the reflex. We conclude that, in male cats, estrogen can only attenuate the exercise pressor reflex in concentrations that exceed the physiological level.

Gadolinium attenuates exercise pressor reflex in cats

2001 ◽  
Vol 280 (5) ◽  
pp. H2153-H2161 ◽  
Author(s):  
Shawn G. Hayes ◽  
Marc P. Kaufman
Keyword(s):  
Pressor Response ◽  
Oxygen Demand ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Mechanical Stimuli ◽  
Group Iii ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Triceps Surae Muscles

The exercise pressor reflex, which arises from the contraction-induced stimulation of group III and IV muscle afferents, is widely believed to be evoked by metabolic stimuli signaling a mismatch between blood/oxygen demand and supply in the working muscles. Nevertheless, mechanical stimuli may also play a role in evoking the exercise pressor reflex. To determine this role, we examined the effect of gadolinium, which blocks mechanosensitive channels, on the exercise pressor reflex in both decerebrate and α-chloralose-anesthetized cats. We found that gadolinium (10 mM; 1 ml) injected into the femoral artery significantly attenuated the reflex pressor responses to static contraction of the triceps surae muscles and to stretch of the calcaneal (Achilles) tendon. In contrast, gadolinium had no effect on the reflex pressor response to femoral arterial injection of capsaicin (5 μg). In addition, gadolinium significantly attenuated the responses of group III muscle afferents, many of which are mechanically sensitive, to both static contraction and to tendon stretch. Gadolinium, however, had no effect on the responses of group IV muscle afferents, many of which are metabolically sensitive, to either static contraction or to capsaicin injection. We conclude that mechanical stimuli arising in contracting skeletal muscles contribute to the elicitation of the exercise pressor reflex.

scholarly journals Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans

2015 ◽  
Vol 309 (9) ◽  
pp. H1479-H1489 ◽  
Author(s):  
Simranjit K. Sidhu ◽  
Joshua C. Weavil ◽  
Massimo Venturelli ◽  
Matthew J. Rossman ◽  
Benjamin S. Gmelch ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Cardiovascular Response ◽  
Knee Extensor ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Group Iii ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Exercise Induced ◽  
The Impact

We investigated the influence of aging on the group III/IV muscle afferents in the exercise pressor reflex-mediated cardiovascular response to rhythmic exercise. Nine old (OLD; 68 ± 2 yr) and nine young (YNG; 24 ± 2 yr) males performed single-leg knee extensor exercise (15 W, 30 W, 80% max) under control conditions and with lumbar intrathecal fentanyl impairing feedback from group III/IV leg muscle afferents. Mean arterial pressure (MAP), cardiac output, leg blood flow (QL), systemic (SVC) and leg vascular conductance (LVC) were continuously determined. With no hemodynamic effect at rest, fentanyl blockade during exercise attenuated both cardiac output and QL ∼17% in YNG, while the decrease in cardiac output in OLD (∼5%) was significantly smaller with no impact on QL ( P = 0.8). Therefore, in the face of similar significant ∼7% reduction in MAP during exercise with fentanyl blockade in both groups, LVC significantly increased ∼11% in OLD, but decreased ∼8% in YNG. The opposing direction of change was reflected in SVC with a significant ∼5% increase in OLD and a ∼12% decrease in YNG. Thus while cardiac output seems to account for the majority of group III/IV-mediated MAP responses in YNG, the impact of neural feedback on the heart may decrease with age and alterations in SVC become more prominent in mediating the similar exercise pressor reflex in OLD. Interestingly, in terms of peripheral hemodynamics, while group III/IV-mediated feedback plays a clear role in increasing LVC during exercise in the YNG, these afferents seem to actually reduce LVC in OLD. These peripheral findings may help explain the limited exercise-induced peripheral vasodilation often associated with aging.

Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat

1998 ◽  
Vol 85 (4) ◽  
pp. 1583-1592 ◽  
Author(s):  
Dave A. MacLean ◽  
Kathryn F. LaNoue ◽  
Kristen S. Gray ◽  
Lawrence I. Sinoway
Keyword(s):  
Muscle Afferents ◽  
Decerebrate Cat ◽  
Exercise Pressor Reflex ◽  
Interstitial Concentration ◽  
Pressor Responses ◽  
Pressor Reflex ◽  
Lactate Levels ◽  
First Time ◽  
Made In ◽  
Stimulation Of

We used the microdialysis technique to measure the interstitial concentration of several putative metabolic stimulants of the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 ± 5 beats/min and 21 ± 8 mmHg and 27 ± 9 beats/min and 37 ± 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned to baseline after 10 min of recovery. Interstitial lactate rose ( P < 0.05) by 0.41 ± 0.15 and 0.56 ± 0.16 mM for the 3- and 5-Hz stimulation protocols, respectively, and were not statistically different from one another. Interstitial lactate levels remained above ( P < 0.05) baseline during recovery in the 5-Hz group. Dialysate phosphate concentrations (corrected for shifts in probe recovery) rose with stimulation ( P < 0.05) by 0.19 ± 0.08 and 0.11 ± 0.03 mM for the 3- and 5-Hz protocols. There were no differences between groups. The resting dialysate K+ concentrations for the 3- and 5-Hz conditions were 4.0 ± 0.1 and 3.9 ± 0.1 meq/l, respectively. During stimulation the dialysate K+ concentrations rose steadily for both conditions, and the increase from rest to stimulation ( P < 0.05) was 0.57 ± 0.19 and 0.81 ± 0.06 meq/l for the 3- and 5-Hz conditions, respectively, with no differences between groups. Resting dialysate pH was 6.915 ± 0.055 and 6.981 ± 0.032 and rose to 7.013 ( P < 0.05) and 7.053 ( P < 0.05) for the 3- and 5-Hz conditions, respectively, and then became acidotic (6.905, P < 0.05) during recovery (5 Hz only). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These data suggest that interstitial K+ and phosphate, but not lactate and H+, may contribute to the stimulation of thin fiber muscle afferents during contraction.

Role played by purinergic receptors on muscle afferents in evoking the exercise pressor reflex

2003 ◽  
Vol 94 (4) ◽  
pp. 1437-1445 ◽  
Author(s):  
Ramy L. Hanna ◽  
Marc P. Kaufman
Keyword(s):  
Receptor Antagonist ◽  
Pressor Response ◽  
Muscle Afferents ◽  
P2 Receptors ◽  
Triceps Surae ◽  
P2 Receptor ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Triceps Surae Muscles

The exercise pressor reflex is believed to be evoked, in part, by multiple metabolic stimuli that are generated when blood supply to exercising muscles is inadequate to meet metabolic demand. Recently, ATP, which is a P2 receptor agonist, has been suggested to be one of the metabolic stimuli evoking this reflex. We therefore tested the hypothesis that blockade of P2 receptors within contracting skeletal muscle attenuated the exercise pressor reflex in decerebrate cats. We found that popliteal arterial injection of pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS; 10 mg/kg), a P2 receptor antagonist, attenuated the pressor response to static contraction of the triceps surae muscles. Specifically, the pressor response to contraction before PPADS averaged 36 ± 3 mmHg, whereas afterward it averaged 14 ± 3 mmHg ( P < 0.001; n = 19). In addition, PPADS attenuated the pressor response to postcontraction circulatory occlusion ( P < 0.01; n = 11). In contrast, popliteal arterial injection of CGS-15943 (250 μg/kg), a P1 receptor antagonist, had no effect on the pressor response to static contraction of the triceps surae muscles. In addition, popliteal arterial injection of PPADS but not CGS-15943 attenuated the pressor response to stretch of the calcaneal (Achilles) tendon. We conclude that P2 receptors on the endings of thin fiber muscle afferents play a role in evoking both the metabolic and mechanoreceptor components of the exercise pressor reflex.

scholarly journals Blockade of the TP receptor attenuates the exercise pressor reflex in decerebrated rats with chronic femoral artery occlusion

2011 ◽  
Vol 301 (5) ◽  
pp. H2140-H2146 ◽  
Author(s):  
Anna K. Leal ◽  
Jennifer L. McCord ◽  
Hirotsugu Tsuchimochi ◽  
Marc P. Kaufman
Keyword(s):  
Peripheral Artery Disease ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Tp Receptor ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Artery Disease

Cyclooxygenase metabolites stimulate or sensitize group III and IV muscle afferents, which comprise the sensory arm of the exercise pressor reflex. The thromboxane (TP) receptor binds several of these metabolites, whose concentrations in the muscle interstitium are increased by exercise under freely perfused conditions and even more so under ischemic conditions, which occur in peripheral artery disease. We showed that the exercise pressor reflex is greater in rats with simulated peripheral artery disease than in rats with freely perfused limbs. These findings prompted us to test the hypothesis that the TP receptor contributes to the exaggerated exercise pressor reflex occurring in a rat model of peripheral artery disease. We compared the cardiovascular responses to static contraction and stretch before and after femoral arterial injections of daltroban (80 μg), a TP receptor antagonist. We performed these experiments in decerebrate rats whose femoral arteries were ligated 72 h before the experiment (a model of simulated peripheral artery disease) and in control rats whose hindlimbs were freely perfused. Daltroban reduced the pressor response to static contraction in both freely perfused ( n = 6; before: Δ12 ± 2 mmHg, after: Δ6 ± 2 mmHg, P = 0.024) and 72-h-ligated rats ( n = 10; before: Δ25 ± 3 mmHg, after: Δ7 ± 4 mmHg, P = 0.001). Likewise, daltroban reduced the pressor response to stretch in the freely perfused group ( n = 9; before: Δ30 ± 3 mmHg, after: Δ17 ± 3 mmHg, P < 0.0001) and in the ligated group ( n = 11; before: Δ37 ± 5 mmHg, after: Δ23 ± 3 mmHg, P = 0.016). Intravenous injections of daltroban had no effect on the pressor response to contraction. We conclude that the TP receptor contributes to the pressor responses evoked by contraction and stretch in both freely perfused rats and rats with simulated peripheral artery disease.

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