scholarly journals Exaggerated exercise pressor reflex in a mouse model of femoral artery ligation

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Qinglu Li ◽  
Mary Garry
Keyword(s):  
Mouse Model ◽  
Femoral Artery ◽  
Artery Ligation ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex

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 Femoral artery ligation increases the responses of thin-fiber muscle afferents to contraction

2015 ◽  
Vol 113 (10) ◽  
pp. 3961-3966 ◽  
Author(s):  
Audrey J. Stone ◽  
Steven W. Copp ◽  
Jennifer L. McCord ◽  
Marc P. Kaufman
Keyword(s):  
Femoral Artery ◽  
Muscle Afferents ◽  
Group Iv ◽  
Artery Ligation ◽  
Thin Fiber ◽  
Group Iii ◽  
Exercise Pressor Reflex ◽  
Hindlimb Muscles ◽  
Static Contraction ◽  
Pressor Reflex

Previous evidence has shown that ligating the femoral artery for 72 h resulted in an exaggerated exercise pressor reflex. To provide electrophysiological evidence for this finding, we examined in decerebrated rats whose femoral arteries were either freely perfused or ligated for 72 h the responses of thin-fiber (i.e., groups III and IV) afferents to static contraction of the hindlimb muscles. We found that contraction increased the combined activity of group III and IV afferents in both freely perfused ( n = 29; baseline: 0.3 ± 0.1 imp/s, contraction: 0.8 ± 0.2 imp/s; P < 0.05) and ligated rats ( n = 28; baseline: 0.4 ± 0.1 imp/s, contraction: 1.4 ± 0.1 imp/s; P < 0.05). Most importantly, the contraction-induced increase in afferent activity was greater in ligated rats than it was in freely perfused rats ( P = 0.005). In addition, the responses of group III afferents to contraction in ligated rats ( n = 15; baseline 0.3 ± 0.1 imp/s, contraction 1.5 ± 0.2 imp/s) were greater ( P = 0.024) than the responses to contraction in freely perfused rats ( n = 18; baseline 0.3 ± 0.1 imp/s, contraction 0.9 ± 0.2 imp/s). Likewise, the responses of group IV afferents to contraction in ligated rats ( n = 13; baseline 0.5 ± 0.1 imp/s, contraction 1.3 ± 0.2 imp/s) were greater ( P = 0.048) than the responses of group IV afferents in freely perfused rats ( n = 11; baseline 0.3 ± 0.1 imp/s, contraction 0.6 ± 0.2 imp/s). We conclude that both group III and IV afferents contribute to the exaggeration of the exercise pressor reflex induced by femoral artery ligation.

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.

scholarly journals Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

2017 ◽  
Vol 44 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Jihong Xing ◽  
Jianhua Li
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Contraction ◽  
Femoral Artery ◽  
Transient Receptor Potential ◽  
Drg Neurons ◽  
Artery Ligation ◽  
Exercise Pressor Reflex ◽  
Arterial Blood ◽  
Pressor Reflex

Background/Aims: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex. Methods: A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues were obtained to examine the protein levels of PAR2 using western blot analysis. Current responses induced by activation of TRPA1 in skeletal muscle DRG neurons were characterized using whole-cell patch clamp methods. The blood pressure response to static exercise (i.e., muscle contraction) and stimulation of TRPA1 was also examined after a blockade of PAR2. Results: The expression of PAR2 was amplified in DRG neurons of the occluded limb, and PAR2 activation with SL-NH2 (a PAR2 agonist) increased the amplitude of TRPA1 currents to a greater degree in DRG neurons of the occluded limb. Moreover, FSLLRY-NH2 (a PAR antagonist) injected into the arterial blood supply of the hindlimb muscles significantly attenuated the pressor response to muscle contraction and TRPA1 stimulation in rats with occluded limbs. Conclusions: The PAR2 signal in muscle sensory nerves contributes to the amplified exercise pressor reflex via TRPA1 mechanisms in rats with femoral artery ligation. These findings provide a pathophysiological basis for autonomic responses during exercise activity in PAD, which may potentially aid in the development of therapeutic approaches for improvement of blood flow in this disease.

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