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 Peripheral μ-opioid receptors attenuate the augmented exercise pressor reflex in rats with chronic femoral artery occlusion

2010 ◽  
Vol 299 (2) ◽  
pp. H557-H565 ◽  
Author(s):  
Hirotsugu Tsuchimochi ◽  
Jennifer L. McCord ◽  
Marc P. Kaufman
Keyword(s):  
Opioid Receptors ◽  
Abdominal Aorta ◽  
Femoral Artery ◽  
Pressor Response ◽  
Inhibitory Effect ◽  
Femoral Arteries ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Μ Opioid Receptors ◽  
Stimulation Of

Recently, opioid receptors have been shown to be expressed on group III and IV afferents, which comprise the sensory arm of the exercise pressor reflex. Although the stimulation of opioid receptors in the central nervous system has been shown to attenuate the exercise pressor reflex, the effect on the reflex of their stimulation in the periphery is unknown. We therefore tested the hypothesis that the activation of peripheral μ-opioid receptors attenuates the exercise pressor reflex. The pressor responses to static contraction were compared before and after the injection of the μ-opioid receptor agonist [d-Ala2, N-MePhe4,Gly-ol5]enkephalin (DAMGO; 1 μg) into the abdominal aorta of decerebrated rats in which one femoral artery had been occluded 72 h previously ( n = 10) and in control rats whose femoral arteries were freely perfused ( n = 8). DAMGO attenuated the peak pressor response to contraction in rats whose femoral arteries had been occluded (before: increase of 34 ± 3 mmHg and after: increase of 22 ± 2 mmHg, P = 0.008); the inhibitory effect of DAMGO was prevented by the injection of naloxone (100 μg) into the abdominal aorta (before: increase of 29 ± 5 mmHg and after: increase of 29 ± 5 mmHg, P = 0.646, n = 7). An intravenous injection of DAMGO (1 μg, n = 6) had no effect on the peak pressor response to contraction in both groups of rats. DAMGO had no effect on the peak pressor response to contraction in rats whose femoral arteries were freely perfused (before: Δ 23 ± 4 mmHg, after: Δ 23 ± 3 mmHg, n = 6) but appeared to have a small effect on topography of the response. DAMGO had no effect on the peak pressor response to tendon stretch in both groups of rats (both P > 0.05). We conclude that the stimulation of peripheral μ-opioid receptors attenuates the exercise pressor reflex in rats whose femoral arteries have been ligated for 72 h.

scholarly journals Investigation of the mechanisms of cyclooxygenase-mediated mechanoreflex sensitization in a rat model of simulated peripheral artery disease

2019 ◽  
Vol 317 (5) ◽  
pp. H1050-H1061 ◽  
Author(s):  
Alec L. E. Butenas ◽  
Tyler D. Hopkins ◽  
Korynne S. Rollins ◽  
Kennedy P. Felice ◽  
Steven W. Copp
Keyword(s):  
Skeletal Muscle ◽  
Peripheral Artery Disease ◽  
Femoral Artery ◽  
Skeletal Muscles ◽  
Pressor Response ◽  
Peripheral Artery ◽  
Artery Ligation ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease

Mechanical and metabolic stimuli within contracting skeletal muscles reflexly increase sympathetic nervous system activity and blood pressure. That reflex, termed the exercise pressor reflex, is exaggerated in patients with peripheral artery disease (PAD) and in a rat PAD model with a chronically ligated femoral artery. The cyclooxygenase (COX) pathway contributes to the exaggerated pressor response during rhythmic skeletal muscle contractions in patients with PAD, but the specific mechanism(s) of the COX-mediated exaggeration are not known. In decerebrate, unanesthetized rats with a chronically ligated femoral artery (“ligated” rats), we hypothesized that hindlimb arterial injection of the COX inhibitor indomethacin would reduce the pressor response during 1-Hz dynamic hindlimb skeletal muscle stretch; a model of the activation of the mechanical component of the exercise pressor reflex (i.e., the mechanoreflex). In ligated rats ( n = 7), indomethacin reduced the pressor response during stretch (control: 30 ± 4; indomethacin: 12 ± 3 mmHg; P < 0.01), whereas there was no effect in rats with “freely perfused” femoral arteries ( n = 6, control: 18 ± 5; indomethacin: 17 ± 5 mmHg; P = 0.87). In ligated rats ( n = 4), systemic indomethacin injection had no effect on the pressor response during stretch. Femoral artery ligation had no effect on skeletal muscle COX protein expression or activity or concentration of the COX metabolite prostaglandin E2. Conversely, femoral artery ligation increased expression of the COX metabolite receptors endoperoxide 4 and thromboxane A2-R in dorsal root ganglia tissue. We conclude that, in ligated rats, the COX pathway sensitizes the peripheral endings of mechanoreflex afferents, which occurs principally as a result of increased expression of COX metabolite receptors. NEW & NOTEWORTHY We demonstrate that the mechanoreflex is sensitized by the cyclooxygenase (COX) pathway within hindlimb skeletal muscles in the rat chronic femoral artery ligation model of simulated peripheral artery disease (PAD). The mechanism of sensitization appears attributable to increased receptors for COX metabolites on sensory neurons and not increased concentration of COX metabolites. Our data may carry important clinical implications for patients with PAD who demonstrate exaggerated increases in blood pressure during exercise compared with healthy counterparts.

scholarly journals Role played by interleukin-6 in evoking the exercise pressor reflex in decerebrate rats: effect of femoral artery ligation

2015 ◽  
Vol 309 (1) ◽  
pp. H166-H173 ◽  
Author(s):  
Steven W. Copp ◽  
Audrey J. Stone ◽  
Jianhua Li ◽  
Marc P. Kaufman
Keyword(s):  
Muscle Contraction ◽  
Femoral Artery ◽  
Pressor Response ◽  
Arterial Supply ◽  
Artery Ligation ◽  
Femoral Arteries ◽  
Exercise Pressor Reflex ◽  
Hindlimb Muscle ◽  
Endogenous Role ◽  
Pressor Reflex

IL-6 signaling via the soluble IL-6 receptor (sIL-6r) has been shown to increase primary afferent responsiveness to noxious stimuli. This finding prompted us to test the hypothesis that IL-6 and sIL-6r would increase the exercise pressor reflex in decerebrate rats with freely perfused femoral arteries. We also tested the hypothesis that soluble glycoprotein (sgp)130, an inhibitor of IL-6/sIL-6r signaling, would decrease the exaggerated exercise pressor reflex that is found in decerebrate rats with ligated femoral arteries. In rats with freely perfused femoral arteries, coinjection of 50 ng of IL-6 and sIL-6r into the arterial supply of the hindlimb significantly increased the peak pressor response to static (control: 14 ± 3 mmHg and IL-6/sIL-6r: 17 ± 2 mmHg, P = 0.03) and intermittent isometric (control: 10 ± 2 mmHg and IL-6/sIL-6r: 15 ± 4 mmHg, P = 0.03) hindlimb muscle contraction. In rats with ligated femoral arteries, injection of 50 ng of sgp130 into the arterial supply of the hindlimb reduced the peak pressor response to static (control: 24 ± 2 mmHg and sgp130: 16 ± 3 mmHg, P = 0.01) and intermittent isometric (control: 16 ± 2 mmHg and sgp130: 13 ± 2 mmHg, P = 0.04) hindlimb muscle contraction, whereas there was no effect of sgp130 on the exercise pressor reflex in rats with freely perfused femoral arteries. We conclude that coinjection of exogenous IL-6 and sIL-6r increased the exercise pressor reflex in rats with freely perfused femoral arteries. More importantly, we also conclude that IL-6 and sIL-6r play an endogenous role in evoking the exercise pressor reflex in rats with ligated femoral arteries but not in rats with freely perfused femoral arteries.

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 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.

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.

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.

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.

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