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.

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 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 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.

ATP stimulates chemically sensitive and sensitizes mechanically sensitive afferents

2002 ◽  
Vol 283 (6) ◽  
pp. H2636-H2643 ◽  
Author(s):  
Jianhua Li ◽  
Lawrence I. Sinoway
Keyword(s):  
Blood Pressure ◽  
Receptor Antagonist ◽  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
P2x Receptors ◽  
Triceps Surae ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Muscle Stretch ◽  
Arterial Blood

We examined whether ATP stimulation of P2X purinoceptors would raise blood pressure in decerebrate cats. Femoral arterial injection of the P2X receptor agonist α,β-methylene ATP into the blood supply of the triceps surae muscle induced a dose-dependent increase in arterial blood pressure. The maximal increase in mean arterial pressure (MAP) evoked by 0.1, 0.2, and 0.5 mM α,β-methylene ATP (0.5 ml/min injection rate) was 6.2 ± 2.5, 22.5 ± 4.4, and 35.2 ± 3.9 mmHg, respectively. The P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (2 mM ia) attenuated the increase in MAP elicited by intra-arterial α,β-methylene ATP (0.5 mM), whereas the P2Y receptor antagonist reactive blue 2 (2 mM ia) did not affect the MAP response to α,β-methylene ATP. In a second group of experiments, we tested the hypothesis that ATP acting through P2X receptors would sensitize muscle afferents and, thereby, augment the blood pressure response to muscle stretch. Two kilograms of muscle stretch evoked a 26.5 ± 4.3 mmHg increase in MAP. This MAP response was enhanced when 2 mM ATP or 0.1 mM α,β-methylene ATP (0.5 ml/min) was arterially infused 10 min before muscle stretch. Furthermore, this effect of ATP on the pressor response to stretch was attenuated by 2 mM pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid ( P < 0.05) but not by the P1 purinoceptor antagonist 8-( p-sulfophenyl)-theophylline (2 mM). These data indicate that activation of ATP-sensitive P2X receptors evokes a skeletal muscle afferent-mediated pressor response and that ATP at relatively low doses enhances the muscle pressor response to stretch via engagement of P2X receptors.

Comparative responses to α,β-methylene-ATP in cat pulmonary, mesenteric, and hindquarter vascular beds

2002 ◽  
Vol 93 (4) ◽  
pp. 1287-1295 ◽  
Author(s):  
Trinity J. Bivalacqua ◽  
Hunter C. Champion ◽  
Mrugeshkumar K. Shah ◽  
Bracken J. De Witt ◽  
Edward W. Inscho ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Pyridoxal Phosphate ◽  
Pressor Response ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Flow Conditions ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Pressor Activity ◽  
Vascular Beds

Responses to the P2X-purinoceptor agonist α,β-methylene-ATP (α,β-MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular beds in the cat. Under constant-flow conditions, injections of α,β-MeATP caused dose-related increases in perfusion pressure in the pulmonary and hindquarter beds and a biphasic response in the mesenteric circulation. In the pulmonary vascular bed, the order of potency was α,β-MeATP > U-46619 > angiotensin II, whereas, in the hindquarters, the order of potency was angiotensin II > U-46619 > α,β-MeATP. The order of potency was similar in the hindquarter and mesenteric beds when the pressor component of the response to α,β-MeATP was compared with responses to angiotensin II and U-46619. The P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid attenuated the pressor response to α,β-MeATP in the hindquarter circulation and the pressor component in the mesenteric vascular bed. Pressor responses to α,β-MeATP were not altered by cyclooxygenase, α-adrenergic, or angiotensin AT1 antagonists. These data show that α,β-MeATP has potent pressor activity in the pulmonary circulation, where it was 100-fold more potent than angiotensin II. In contrast, α,β-MeATP had modest pressor activity in the systemic bed, where it was 1,000-fold less potent than angiotensin II. These data suggest that responses to α,β-MeATP are dependent on the vascular bed studied and may be dependent on the density of P2X receptors in the vascular bed.

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 Intrathecal injection of brilliant blue G, a P2X7 antagonist, attenuates the exercise pressor reflex in rats

2020 ◽  
Vol 319 (2) ◽  
pp. R223-R232
Author(s):  
Juan A. Estrada ◽  
Guillaume P. Ducrocq ◽  
Joyce S. Kim ◽  
Marc P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Pressor Response ◽  
Intrathecal Injection ◽  
P2x Receptors ◽  
Brilliant Blue ◽  
Brilliant Blue G ◽  
P2x7 Receptors ◽  
P2x3 Receptors ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex

Purinergic 2X (P2X) receptors on the endings of group III and IV afferents play a role in evoking the exercise pressor reflex. Particular attention has been paid to P2X3 receptors because their blockade in the periphery attenuated this reflex. In contrast, nothing is known about the role played by P2X receptors in the spinal cord in evoking the exercise pressor reflex in rats. P2X7 receptors, in particular, may be especially important in this regard because they are found in abundance on spinal glial cells and may communicate with neurons to effect reflexes controlling cardiovascular function. Consequently, we investigated the role played by spinal P2X7 receptors in evoking the exercise pressor reflex in decerebrated rats. We found that intrathecal injection of the P2X7 antagonist brilliant blue G (BBG) attenuated the exercise pressor reflex (blood pressure index: 294 ± 112 mmHg·s before vs. 7 ± 32 mmHg·s after; P < 0.05). Likewise, intrathecal injection of minocycline, which inhibits microglial cell output, attenuated the reflex. In contrast, intrathecal injection of BBG did not attenuate the pressor response evoked by intracarotid injection of sodium cyanide, a maneuver that stimulated carotid chemoreceptors. Moreover, injections of BBG either into the arterial supply of the contracting hindlimb muscles or into the jugular vein did not attenuate the exercise pressor reflex. Our findings support the hypothesis that P2X7 receptors on microglial cells within the spinal cord play a role in evoking 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.

scholarly journals Functional knockout of ASIC3 attenuates the exercise pressor reflex in decerebrated rats with ligated femoral arteries

2020 ◽  
Vol 318 (5) ◽  
pp. H1316-H1324
Author(s):  
Joyce S. Kim ◽  
Guillaume P. Ducrocq ◽  
Marc P. Kaufman
Keyword(s):  
Pressor Response ◽  
Genetic Approach ◽  
Wild Type ◽  
Femoral Arteries ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex

We used a genetic approach to test the hypothesis that the magnitude of the exercise pressor reflex evoked in ligated ASIC3 KO rats was significantly lower than the magnitude of the exercise pressor reflex evoked in their ligated wild-type (WT) counterparts. The pressor response to contraction in ligated ASIC3 KO rats was significantly smaller than was the pressor response to contraction in ligated WT rats.

scholarly journals Cloning and characterization of a functional P2X receptor from larval bullfrog skin

2001 ◽  
Vol 281 (3) ◽  
pp. C954-C962 ◽  
Author(s):  
Philip J. Jensik ◽  
Doyle Holbird ◽  
Michael W. Collard ◽  
Thomas C. Cox
Keyword(s):  
Pyridoxal Phosphate ◽  
Rana Catesbeiana ◽  
Short Circuit ◽  
Short Circuit Current ◽  
P2x Receptors ◽  
P2x Receptor ◽  
Disulfonic Acid ◽  
Acid Protein ◽  
Sensory Reception ◽  
Tadpole Skin

ATP activates an apical-to-basolateral nonselective cation current across the skin of larval bullfrogs ( Rana catesbeiana) with similarities to currents carried by some P2X receptors. A functional P2X receptor was cloned from tadpole skin RNA that encodes a 409-amino acid protein with highest protein homology to cP2X8. RT-PCR showed that this transcript was found in skin, heart, eye, brain, and skeletal muscle of tadpoles but not in skin, brain, or heart of adults. After transcribed RNA from this clone was injected into Xenopus oocytes, application of ATP activated a transient current similar to other P2X receptors and the ATP-activated transient in short-circuit current ( I sc) across intact skin. The agonists 2-methylthio-ATP and adenosine-5′- O-(thiotriphoshate) also activated transient currents. α,β-Methylene-ATP and ADP were poor agonists of this receptor. Suramin and pyridoxal phosphate 6-azophenyl-2′,4′-disulfonic acid tetrasodium (PPADS) were potent antagonists, and PPADS showed an irreversible blockade of this receptor to agonist activation. Under external Na+-free, Ca2+/Mg2+-free conditions ( N-methyl-d-glucamine replacement, 0.5 mM EGTA), ATP activated a steadily increasing inward current. Fluorescence microscopy showed that propidium was entering the cells, suggesting that a relatively large pore size was formed under zero divalent conditions. This clone has some characteristics consistent with previously described ATP-activated I sc in the tadpole skin. Because the clone is not found in adult skin, it may have some exclusive role in the tadpole such as sensory reception by the skin or triggering apoptosis at metamorphosis.

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