α,β-Methylene ATP elicits a reflex pressor response arising from muscle in decerebrate cats

2002 ◽  
Vol 93 (3) ◽  
pp. 834-841 ◽  
Author(s):  
Ramy L. Hanna ◽  
Shawn G. Hayes ◽  
Marc P. Kaufman
Keyword(s):  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
P2 Receptors ◽  
Vascular Supply ◽  
Disulfonic Acid ◽  
Exercise Pressor Reflex ◽  
Pressor Responses ◽  
Chemical Stimuli ◽  
Pressor Reflex ◽  
Stimulation Of

In part, the exercise pressor reflex is believed to be evoked by chemical stimuli signaling that blood supply to exercising muscles is not adequate to meet its metabolic demands. There is evidence that either ATP or adenosine may function as one of these chemical stimuli. For example, muscle interstitial concentrations of both substances have been found to increase during exercise. This finding led us to test the hypothesis that popliteal arterial injection of α,β-methylene ATP (5, 20, and 50 μg/kg), which stimulates P2X receptors, and 2-chloroadenosine (25 μg/kg), which stimulates P1 receptors, evokes reflex pressor responses in decerebrate, unanesthetized cats. We found that popliteal arterial injection of the two highest doses of α,β-methylene ATP evoked pressor responses, whereas popliteal arterial injection of 2-chloroadenosine did not. In addition, the pressor responses evoked by α,β-methylene ATP were blocked either by section of the sciatic nerve or by prior popliteal arterial injection of pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (10 mg/kg), a selective P2-receptor antagonist. We conclude that the stimulation of P2 receptors, which are accessible through the vascular supply of skeletal muscle, evokes reflex pressor responses. In addition, our findings are consistent with the hypothesis that the stimulation of P2 receptors comprises part of the metabolic error signal evoking the exercise pressor reflex.

scholarly journals Purinergic 2X receptors play a role in evoking the exercise pressor reflex in rats with peripheral artery insufficiency

2014 ◽  
Vol 306 (3) ◽  
pp. H396-H404 ◽  
Author(s):  
Audrey J. Stone ◽  
Katsuya Yamauchi ◽  
Marc P. Kaufman
Keyword(s):  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Femoral Arteries ◽  
Exercise Pressor Reflex ◽  
Pressor Responses ◽  
Before And After ◽  
Pressor Reflex

Purinergic 2X (P2X) receptors on the endings of thin fiber afferents have been shown to play a role in evoking the exercise pressor reflex in cats. In this study, we attempted to extend this finding to decerebrated, unanesthetized rats whose femoral arteries were either freely perfused or were ligated 72 h before the start of the experiment. We first established that our dose of pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS; 10 mg/kg), a P2X receptor antagonist, attenuated the pressor response to α,β-methylene ATP (10 μg/kg), a P2X receptor agonist. We then compared the exercise pressor reflex before and after infusing PPADS into the arterial supply of the hindlimb muscles that were statically contracted. In rats with freely perfused femoral arteries, the peak pressor responses to contraction were not significantly attenuated by PPADS (before PPADS: 19 ± 2 mmHg, 13 min after PPADS: 17 ± 2 mmHg, and 25 min after PPADS: 17 ± 3 mmHg). Likewise, the cardioaccelerator and renal sympathetic nerve responses were not significantly attenuated. In contrast, we found that in rats whose femoral arteries were ligated PPADS significantly attenuated the peak pressor responses to contraction (before PPADS: 37 ± 5 mmHg, 13 min after PPADS: 27 ± 6 mmHg, and 25 min after PPADS: 25 ± 5 mmHg; P < 0.05). Heart rate was not significantly attenuated, but renal SNA was at certain time points over the 30-s contraction period. We conclude that P2X receptors play a substantial role in evoking the exercise pressor reflex in rats whose femoral arteries were ligated but play only a minimal role in evoking the reflex in rats whose femoral arteries were freely perfused.

scholarly journals Dorsal root tetrodotoxin-resistant sodium channels do not contribute to the augmented exercise pressor reflex in rats with chronic femoral artery occlusion

2011 ◽  
Vol 300 (2) ◽  
pp. H652-H663 ◽  
Author(s):  
Hirotsugu Tsuchimochi ◽  
Jennifer L. McCord ◽  
Anna K. Leal ◽  
Marc P. Kaufman
Keyword(s):  
Sodium Channels ◽  
Femoral Artery ◽  
Tibial Nerve ◽  
Pressor Response ◽  
Artery Ligation ◽  
Exercise Pressor Reflex ◽  
Tibial Nerve Stimulation ◽  
Pressor Responses ◽  
Pressor Reflex ◽  
Stimulation Of

We investigated the contribution of tetrodotoxin (TTX)-resistant sodium channels to the augmented exercise pressor reflex observed in decerebrated rats with femoral artery ligation. The pressor responses to static contraction, to tendon stretch, and to electrical stimulation of the tibial nerve were compared before and after blocking TTX-sensitive sodium channels on the L3-L6 dorsal roots of rats whose hindlimbs were freely perfused and rats whose femoral arteries were ligated 72 h before the start of the experiment. In the freely perfused group ( n = 9), pressor (Δ22 ± 4 mmHg) and cardioaccelerator (Δ32 ± 6 beats/min) responses to contraction were attenuated by 1 μM TTX (Δ4 ± 1 mmHg, P < 0.05 and Δ17 ± 4 beats/min, P < 0.05, respectively). In the 72 h ligated group ( n = 9), the augmented pressor response to contraction (32 ± 4 mmHg) was also attenuated by 1 μM TTX (Δ8 ± 2 mmHg, P < 0.05). The cardioaccelerator response to contraction was not significantly attenuated in these rats. In addition, TTX suppressed the pressor response to tendon stretch in both groups of rats. Electrical stimulation of the tibial nerve evoked similar pressor responses between the two groups (freely perfused: Δ74 ± 9 mmHg and 72 h ligated: Δ78 ± 5 mmHg). TTX attenuated the pressor response to the tibial nerve stimulation by about one-half in both groups. Application of the TTX-resistant sodium channel blocker A-803467 (1 μM) with TTX (1 μM) did not block the pressor response to tibial nerve stimulation to any greater extent than did application of TTX (1 μM) alone. Although the contribution of TTX-resistant sodium channels to the augmented exercise pressor reflex may be slightly increased in rats with chronic femoral artery ligation, TTX-resistant sodium channels on dorsal roots do not play a major role in the augmented exercise pressor reflex.

scholarly journals Spinal P2X receptor modulates muscle pressor reflex via glutamate

2009 ◽  
Vol 106 (3) ◽  
pp. 865-870 ◽  
Author(s):  
Jianhua Li ◽  
Jian Lu ◽  
Zhaohui Gao ◽  
Satoshi Koba ◽  
Jihong Xing ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Pressor Reflex ◽  
Stimulation Of

Static contraction of skeletal muscle evokes reflex increases in blood pressure and heart rate. Previous studies showed that P2X receptors located at the dorsal horn of the spinal cord play a role in modulating the muscle pressor reflex. P2X stimulation can alter release of the excitatory amino acid, glutamate (Glu). In this report, we tested the hypothesis that stimulation of P2X receptors enhances the concentrations of Glu ([Glu]) in the dorsal horn, and that blocking P2X receptors attenuates contraction-induced Glu increases and the resultant reflex pressor response. Contraction was elicited by electrical stimulation of the L7 and S1 ventral roots of 14 cats. Glu samples were collected from microdialysis probes inserted in the L7 level of the dorsal horn of the spinal cord, and dialysate [Glu] was determined using the HPLC method. First, microdialyzing α,β-methylene ATP (0.4 mM) into the dorsal horn significantly increased [Glu]. In addition, contraction elevated [Glu] from baseline of 536 ± 53 to 1,179 ± 192 nM ( P < 0.05 vs. baseline), and mean arterial pressure by 39 ± 8 mmHg in the control experiment. Microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (10 mM) into the dorsal horn attenuated the contraction induced-Glu increase (610 ± 128 to 759 ± 147 nM; P > 0.05) and pressor response (16 ± 3 mmHg, P < 0.05 vs. control). Our findings demonstrate that P2X modulates the cardiovascular responses to static muscle contraction by affecting the release of Glu in the dorsal horn of the spinal cord.

scholarly journals Effects of peripheral and spinal κ-opioid receptor stimulation on the exercise pressor reflex in decerebrate rats

2014 ◽  
Vol 307 (3) ◽  
pp. R281-R289 ◽  
Author(s):  
Steven W. Copp ◽  
Audrey J. Stone ◽  
Katsuya Yamauchi ◽  
Marc P. Kaufman
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Pressor Response ◽  
Intrathecal Injection ◽  
Muscle Afferents ◽  
Femoral Arteries ◽  
Exercise Pressor Reflex ◽  
Pressor Responses ◽  
Pressor Reflex ◽  
Stimulation Of

The exercise pressor reflex is greater in rats with ligated femoral arteries than it is in rats with freely perfused femoral arteries. The exaggerated reflex in rats with ligated arteries is attenuated by stimulation of μ-opioid and δ-opioid receptors on the peripheral endings of thin-fiber muscle afferents. The effect of stimulation of κ-opioid receptors on the exercise pressor reflex is unknown. We tested the hypothesis that stimulation of κ-opioid receptors attenuates the exercise pressor reflex in rats with ligated, but not freely perfused, femoral arteries. The pressor responses to static contraction were compared before and after femoral arterial or intrathecal injection of the κ-opioid receptor agonist U62066 (1, 10, and 100 μg). Femoral arterial injection of U62066 did not attenuate the pressor responses to contraction in either group of rats. Likewise, intrathecal injection of U62066 did not attenuate the pressor response to contraction in rats with freely perfused femoral arteries. In contrast, intrathecal injection of 10 and 100 μg of U62066 attenuated the pressor response to contraction in rats with ligated femoral arteries, an effect that was blocked by prior intrathecal injection of the κ-opioid receptor antagonist nor-binaltorphimine. In rats with ligated femoral arteries, the pressor response to stimulation of peripheral chemoreceptors by sodium cyanide was not changed by intrathecal U62066 injections, indicating that these injections had no direct effect on the sympathetic outflow. We conclude that stimulation of spinal, but not peripheral, κ-opioid receptors attenuates the exaggerated exercise pressor reflex in rats with ligated femoral arteries.

scholarly journals PPADS does not block contraction-induced prostaglandin E2 synthesis in cat skeletal muscle

2008 ◽  
Vol 295 (5) ◽  
pp. H2043-H2045 ◽  
Author(s):  
Jennifer L. McCord ◽  
Shawn G. Hayes ◽  
Marc P. Kaufman
Keyword(s):  
Skeletal Muscle ◽  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
Triceps Surae ◽  
Prostaglandin E ◽  
Exercise Pressor Reflex ◽  
Before And After ◽  
Pressor Reflex ◽  
Response To Exercise

Pyridoxal-phosphate-6-azophenyl-2′-4-disulfonate (PPADS), a purinergic 2 (P2) receptor antagonist, has been shown to attenuate the exercise pressor reflex in cats. In vitro, however, PPADS has been shown to block the production of prostaglandins, some of which play a role in evoking the exercise pressor reflex. Thus the possibility exists that PPADS blocks the exercise pressor reflex through a reduction in prostaglandin synthesis rather than through the blockade of P2 receptors. Using microdialysis, we collected interstitial fluid from skeletal muscle to determine prostaglandin E2 (PGE2) concentrations during the intermittent contraction of the triceps surae muscle before and after a popliteal arterial injection of PPADS (10 mg/kg). We found that the PGE2 concentration increased in response to the intermittent contraction before and after the injection of PPADS (both, P < 0.05). PPADS reduced the pressor response to exercise ( P < 0.05) but had no effect on the magnitude of PGE2 production during contraction ( P = 0.48). These experiments demonstrate that PPADS does not block the exercise pressor reflex through a reduction in PGE2 synthesis. We suggest that PGE2 and P2 receptors play independent roles in stimulating the exercise pressor reflex.

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

2006 ◽  
Vol 290 (3) ◽  
pp. H1214-H1219 ◽  
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.

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 NADPH oxidase-derived reactive oxygen species in skeletal muscle modulates the exercise pressor reflex

2009 ◽  
Vol 107 (2) ◽  
pp. 450-459 ◽  
Author(s):  
Han-Jun Wang ◽  
Yan-Xia Pan ◽  
Wei-Zhong Wang ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Blood Pressure ◽  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Pressor Response ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Stimulation Of

Muscle metabolic by-products during exercise, such as K+, lactic acid, ATP, H+, and phosphate, are well established to be involved in the reflex cardiovascular response to static muscle contraction. However, the role of muscle reactive oxygen species (ROS), a metabolic by-product during muscle contraction, in the exercise pressor reflex (EPR) has not been investigated in detail. In the present study, we evaluated the role of muscle ROS in the EPR in a decerebrate rat model. We hypothesized that muscle NADPH oxidase-derived ROS contributes to sensitization of the EPR. Thus the rise in blood pressure and heart rate in response to a 30-s static contraction induced by electrical stimulation of L4/L5 ventral roots was compared before and after hindlimb arterial infusion of the redox agents: diethyldithiocarbamate, a superoxide dismutase inhibitor; the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (tempol); the free radical scavenger dimethylthiourea; a NADPH oxidase inhibitor, apocynin; and a xanthine oxidase inhibitor, allopurinol. The EPR-induced pressor response was augmented after treatment with diethyldithiocarbamate and was attenuated after treatment with tempol, dimethylthiourea, and apocynin. Treatment with allopurinol did not affect the EPR function. None of the drug's affected the EPR heart rate response. In addition, neither the pressor response to electrical stimulation of the central end of dorsal roots, nor femoral blood flow was affected by any treatment. These data suggest that NADPH oxidase-derived muscle ROS plays an excitatory role in the EPR control of blood pressure.

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.

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