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.

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 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.

Bradykinin release from contracting skeletal muscle of the cat

1990 ◽  
Vol 69 (4) ◽  
pp. 1225-1230 ◽  
Author(s):  
C. L. Stebbins ◽  
O. A. Carretero ◽  
T. Mindroiu ◽  
J. C. Longhurst
Keyword(s):  
Skeletal Muscle ◽  
Arterial Occlusion ◽  
Triceps Surae ◽  
Strongly Correlated ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Before And After ◽  
Pressor Reflex ◽  
Triceps Surae Muscles ◽  
Induced Changes

Results of previous studies from our laboratory suggest that bradykinin has a role in the exercise pressor reflex elicited by static muscle contraction. The purpose of this study was to quantify the release of bradykinin from contracting skeletal muscle. In 18 cats, blood samples were withdrawn directly from the venous effluent of the triceps surae muscles immediately before and after 30 s of static contraction producing peak muscle tensions of 33, 50, and 100% of maximum electrically stimulated contraction. Contractions producing muscle tensions of 50 and 100% of maximum increased muscle venous bradykinin levels by 27 +/- 9 and 19 +/- 10 pg/ml, respectively. Conversely, 33% maximum contraction did not alter muscle venous bradykinin concentrations. However, when captopril was administered to slow the degradation of bradykinin, muscle venous bradykinin increased from 68 +/- 15 pg/ml at rest to 106 +/- 18 after contractions of 33% of maximum. When muscle ischemia was induced by 2 min of arterial occlusion before and during 30 s of 33% of maximum contraction, muscle venous bradykinin increased by 15 +/- 5 pg/ml. In addition, contraction-induced changes in muscle venous pH and lactate strongly correlated with bradykinin concentrations (r = 0.80 and 0.83, respectively). These data demonstrate that static contraction of relatively high intensity evokes the release of bradykinin from skeletal muscle and that ischemia, decreased pH, and increased lactate are strongly correlated with this release.

scholarly journals Cyclooxygenase inhibition does not impact the pressor response during static or dynamic mechanoreflex activation in healthy decerebrate rats

2019 ◽  
Vol 317 (3) ◽  
pp. R369-R378 ◽  
Author(s):  
Korynne S. Rollins ◽  
Tyler D. Hopkins ◽  
Alec L. Butenas ◽  
Kennedy P. Felice ◽  
Carl J. Ade ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pressor Response ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Prostaglandin E ◽  
Muscle Stretch ◽  
Triceps Surae Muscle ◽  
Cox Inhibitor

Passive limb movement and limb muscle stretch in humans and animals are common experimental strategies used to investigate activation of the muscle mechanoreflex independent of contraction-induced metabolite production. Cyclooxygenase (COX) metabolites, however, are produced by skeletal muscle stretch in vitro and have been found to impact various models of mechanoreflex activation. Whether COX metabolites influence the decerebrate rat triceps surae muscle stretch mechanoreflex model remains unknown. We examined the effect of rat triceps surae muscle stretch on the interstitial concentration of the COX metabolite prostaglandin E2 (PGE2). Interstitial PGE2 concentration was increased above baseline values by 4 min of both static (38% increase, P = 0.01) and dynamic (56% increase, P < 0.01) triceps surae muscle stretch ( n = 10). The 4-min protocol was required to collect enough microdialysis fluid for PGE2 detection. The finding that skeletal muscle stretch in vivo was capable of producing COX metabolites prompted the hypothesis that intra-arterial administration of the COX inhibitor indomethacin (1 mg/kg) would reduce the pressor and cardioaccelerator responses evoked during 30 s (the duration most commonly used in the rat mechanoreflex model) of static and dynamic rat triceps surae muscle stretch. We found that indomethacin had no effect ( P > 0.05, n = 9) on the pressor or cardioaccelerator response during 30 s of either static or dynamic stretch. We conclude that, despite the possibility of increased COX metabolite concentration, COX metabolites do not activate or sensitize thin-fiber muscle afferents stimulated during 30 s of static or dynamic hindlimb skeletal muscle stretch in healthy rats.

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.

Role of NO in modulating neuronal activity in superficial dorsal horn of spinal cord during exercise pressor reflex

2002 ◽  
Vol 283 (3) ◽  
pp. H1012-H1018 ◽  
Author(s):  
Jianhua Li ◽  
Jere H. Mitchell
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Pressor Response ◽  
Triceps Surae ◽  
Superficial Dorsal Horn ◽  
Exercise Pressor Reflex ◽  
Fos Protein ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Fos Expression

Static contraction of hindlimb skeletal muscle in cats induces a reflex pressor response. The superficial dorsal horn of the spinal cord is the major site of the first synapse of this reflex. In this study, static contraction of the triceps surae muscle was evoked by electrical stimulation of the tibial nerve for 2 min in anesthetized cats (stimulus parameters: two times motor threshold at 30 Hz, 0.025-ms duration). Ten stimulations were performed and 1-min rest was allowed between stimulations. Muscle contraction caused a maximal increase of 32 ± 5 mmHg in mean arterial pressure (MAP), which was obtained from the first three contractions. Activated neurons in the superficial dorsal horn were identified by c-Fos protein. Distinct c-Fos expression was present in the L6-S1 level of the superficial dorsal horn ipsilateral to the contracting leg (88 ± 14 labeled cells per section at L7), whereas only scattered c-Fos expression was observed in the contralateral superficial dorsal horn (9 ± 2 labeled cells per section, P < 0.05 compared with ipsilateral section). A few c-Fos-labeled cells were found in control animals (12 ± 5 labeled cells per section, P < 0.05 compared with stimulated cats). Furthermore, double-labeling methods demonstrated that c-Fos protein coexisted with nitric oxide (NO) synthase (NOS) positive staining in the superficial dorsal horn. Finally, an intrathecal injection of an inhibitor of NOS, N-nitro-l-arginine methyl ester (5 mM), resulted in fewer c-Fos-labeled cells (58 ± 12 labeled cells per section) and a reduced maximal MAP response (20 ± 3 mmHg, P < 0.05). These results suggest that the exercise pressor reflex induced by static contraction is mediated by activation of neurons in the superficial dorsal horn and that formation of NO in this region is involved in modulating the activated neurons and the pressor response to contraction.

Sensory neuron inositol-1,4,5-trisphosphate (IP3) receptors contribute to chronic mechanoreflex sensitization in rats with simulated peripheral artery disease

2021 ◽  
Author(s):  
Korynne S. Rollins ◽  
Alec L E Butenas ◽  
Auni C Williams ◽  
Steven W. Copp
Keyword(s):  
Skeletal Muscle ◽  
Receptor Antagonist ◽  
Sensory Neuron ◽  
Peripheral Artery Disease ◽  
Femoral Artery ◽  
Pressor Response ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease

The mechanoreflex is exaggerated in patients with peripheral artery disease (PAD) and in a rat model of simulated PAD in which a femoral artery is chronically (~72hrs) ligated. We found recently that, in rats with a ligated femoral artery, blockade of thromboxane A2 (TxA2) receptors on the sensory endings of thin fiber muscle afferents reduced the pressor response to 1 Hz repetitive/dynamic hindlimb skeletal muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production). Conversely, we found no effect of TxA2 receptor blockade in rats with freely perfused femoral arteries. Here we extended the isolated mechanoreflex findings in "ligated" rats to experiments evoking dynamic hindlimb skeletal muscle contractions. We also investigated the role played by inositol 1-4-5-trisphosphate (IP3) receptors, receptors associated with intracellular signaling linked to TxA2 receptors, in the exaggerated response to dynamic mechanoreflex and exercise pressor reflex activation in ligated rats. Injection of the TxA2 receptor antagonist daltroban into the arterial supply of the hindlimb reduced the pressor response to 1 Hz dynamic contraction in ligated but not "freely perfused" rats. Moreover, injection of the IP3 receptor antagonist xestospongin C into the arterial supply of the hindlimb reduced the pressor response to 1 Hz dynamic stretch and contraction in ligated but not freely perfused rats. These findings demonstrate that, in rats with a ligated femoral artery, sensory neuron TxA2 receptor and IP3 receptor mediated signaling contributes to a chronic sensitization of the mechanically activated channels associated with the mechanoreflex and the exercise pressor reflex.

The exercise pressor reflex is attenuated by intrathecal oxytocin

1994 ◽  
Vol 267 (4) ◽  
pp. R909-R915 ◽  
Author(s):  
C. L. Stebbins ◽  
A. Ortiz-Acevedo
Keyword(s):  
Spinal Cord ◽  
Pressor Response ◽  
Intrathecal Injection ◽  
Sensory Nerve ◽  
Lumbar Spinal Cord ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Before And After ◽  
Pressor Reflex ◽  
Lumbar Spinal

We tested the hypothesis that oxytocin (Oxt) acts in the lumbar spinal cord to attenuate reflex pressor (mean arterial pressure, MAP) and heart rate (HR) responses to static hindlimb contraction (i.e., the exercise pressor reflex). Thus we compared MAP and HR responses to electrically stimulated hindlimb static contraction in the anesthetized cat before and after intrathecal injection of Oxt (30 pmol, n = 3; 300 pmol, n = 6; or 3 nmol, n = 6). The 300-pmol dose was most effective; it attenuated the pressor response to static contraction by 39 +/- 10% but had no effect on HR. In three other cats, contraction-induced increases in MAP and HR were monitored before and after intrathecal injection of 300 pmol of Oxt + 300 nmol of the selective Oxt receptor antagonist [d(CH2)5(1),O-Me-Tyr2,Thr4,Tyr9,Orn8]vasotocin. Pretreatment with the antagonist eliminated the effect of Oxt on MAP. In an additional 10 cats, increases in these same variables in response to static contraction were compared before and after intrathecal injection of the Oxt antagonist (30 nmol, n = 3 or 300 nmol, n = 7) into the lumbar spinal cord (L1-L7). Whereas 30 nmol of the Oxt antagonist had no effect, the 300-nmol dose augmented the contraction-induced pressor and HR responses by 28 +/- 7 and 32 +/- 17%, respectively. These data imply that endogenous Oxt modulates the exercise pressor reflex by its action on Oxt receptors in the lumbar spinal cord that can attenuate sensory nerve transmission from skeletal muscle.

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.

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