Central integration of muscle reflex and arterial baroreflex in midbrain periaqueductal gray: roles of GABA and NO

2004 ◽  
Vol 287 (3) ◽  
pp. H1312-H1318 ◽  
Author(s):  
Jianhua Li
Keyword(s):  
Muscle Contraction ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Periaqueductal Gray ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Reflex Response ◽  
Arterial Baroreflex ◽  
Pressor Reflex ◽  
Change In Mean

It has been suggested that the midbrain periaqueductal gray (PAG) is a neural integrating site for the interaction between the muscle pressor reflex and the arterial baroreceptor reflex. The underlying mechanisms are poorly understood. The purpose of this study was to examine the roles of GABA and nitric oxide (NO) in modulating the PAG integration of both reflexes. To activate muscle afferents, static contraction of the triceps surae muscle was evoked by electrical stimulation of the L7 and S1 ventral roots of 18 anesthetized cats. In the first group of experiments ( n = 6), the pressor response to muscle contraction was attenuated by bilateral microinjection of muscimol (a GABA receptor agonist) into the lateral PAG [change in mean arterial pressure (ΔMAP) = 24 ± 5 vs. 46 ± 8 mmHg in control]. Conversely, the pressor response was significantly augmented by 0.1 mM bicuculline, a GABAA receptor antagonist (ΔMAP = 65 ± 10 mmHg). In addition, the effect of GABAA receptor blockade on the reflex response was significantly blunted after sinoaortic denervation and vagotomy ( n = 4). In the second group of experiments ( n = 8), the pressor response to contraction was significantly attenuated by microinjection of l-arginine into the lateral PAG (ΔMAP = 26 ± 4 mmHg after l-arginine injection vs. 45 ± 7 mmHg in control). The effect of NO attenuation was antagonized by bicuculline and was reduced after denervation. These data demonstrate that GABA and NO within the PAG modulate the pressor response to muscle contraction and that NO attenuation of the muscle pressor reflex is mediated via arterial baroreflex-engaged GABA increase. The results suggest that the PAG plays an important role in modulating cardiovascular responses when muscle afferents are activated.

NO formation in nucleus tractus solitarii attenuates pressor response evoked by skeletal muscle afferents

2001 ◽  
Vol 280 (5) ◽  
pp. H2371-H2379 ◽  
Author(s):  
Jianhua Li ◽  
Jeffrey T. Potts
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Pressor Response ◽  
Extracellular Fluid ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Nucleus Tractus Solitarii ◽  
Triceps Surae ◽  
No Formation ◽  
Fos Protein

We have previously shown that static muscle contraction induces the expression of c-Fos protein in neurons of the nucleus tractus solitarii (NTS) and that some of these cells were codistributed with neuronal NADPH-diaphorase [nitric oxide (NO) synthase]-positive fibers. In the present study, we sought to determine the role of NO in the NTS in mediating the cardiovascular responses elicited by skeletal muscle afferent fibers. Static contraction of the triceps surae muscle was induced by electrical stimulation of the L7 and S1 ventral roots in anesthetized cats. Muscle contraction during microdialysis of artificial extracellular fluid increased mean arterial pressure (MAP) and heart rate (HR) 51 ± 9 mmHg and 18 ± 3 beats/min, respectively. Microdialysis ofl-arginine (10 mM) into the NTS to locally increase NO formation attenuated the increases in MAP (30 ± 7 mmHg, P < 0.05) and HR (14 ± 2 beats/min, P > 0.05) during contraction. Microdialysis ofd-arginine (10 mM) did not alter the cardiovascular responses evoked by muscle contraction. Microdialysis of N G-nitro-l-arginine methyl ester (2 mM) during contraction attenuated the effects ofl-arginine on the reflex cardiovascular responses. These findings demonstrate that an increase in NO formation in the NTS attenuates the pressor response to static muscle contraction, indicating that the NO system plays a role in mediating the cardiovascular responses to static muscle contraction in the NTS.

Muscle pressor reflex: potential role of vanilloid type 1 receptor and acid-sensing ion channel

2004 ◽  
Vol 97 (5) ◽  
pp. 1709-1714 ◽  
Author(s):  
Jianhua Li ◽  
Michael D. Maile ◽  
Adam N. Sinoway ◽  
Lawrence I. Sinoway
Keyword(s):  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Reflex Response ◽  
Arterial Blood ◽  
Afferent Nerves ◽  
Muscle Afferent ◽  
Pressor Reflex ◽  
Stimulation Of

Reflex cardiovascular responses to muscle contraction are mediated by mechanical and metabolic stimulation of thin muscle afferent fibers. Metabolic stimulants and receptors involved in responses are uncertain. Capsaicin depolarizes thin sensory afferent nerves that have vanilloid type 1 receptors (VR1). Among potential endogenous ligands of thin fibers, H+ has been suggested as a metabolite mediating the reflex muscle response as well as a potential stimulant of VR1. It has also been suggested that acid-sensing ion channels (ASIC) mediate H+, evoking afferent nerve excitation. We have examined the roles of VR1 and ASIC in mediating cardiovascular reflex responses to acid stimulation of muscle afferents in a rat model. In anesthetized rats, injections of capsaicin into the arterial blood supply of triceps surae muscles evoked a biphasic response ( n = 6). An initial fall in mean arterial pressure (from baseline of 95.8 ± 9.5 to 70.4 ± 4.5 mmHg, P < 0.05 vs. baseline) was followed by an increase (to 131.6 ± 11.3 mmHg, P < 0.05 vs. baseline). Anandamide (an endogenous substance that activates VR1) induced the same change in blood pressure as did capsaicin. The pressor (but not depressor) component of the response was blocked by capsazepine (a VR1 antagonist) and section of afferent nerves. In decerebrate rats ( n = 8), H+ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker). In rats ( n = 12) pretreated with resiniferatoxin to destroy muscle afferents containing VR1, capsaicin and H+ responses were blunted. We conclude that H+ stimulates ASIC, evoking the reflex response, and that ASIC are likely to be frequently found on afferents containing VR1. The data also suggest that VR1 and ASIC may play a role in processing of muscle afferent signals, evoking the muscle pressor reflex.

NMDA receptor blockade in cat dorsal horn blunts reflex pressor response to muscle contraction and stretch

1996 ◽  
Vol 270 (2) ◽  
pp. H500-H508 ◽  
Author(s):  
G. A. Hand ◽  
A. F. Meintjes ◽  
A. W. Keister ◽  
A. Ally ◽  
L. B. Wilson
Keyword(s):  
Nmda Receptor ◽  
Muscle Contraction ◽  
Nmda Receptors ◽  
Dorsal Horn ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Nmda Receptor Antagonist ◽  
Muscle Afferents ◽  
The Central Nervous System ◽  
Passive Stretch

The role of N-methyl-D-aspartate (NMDA) receptors in the reflex pressor response to static muscle contraction and passive stretch was examined by microdialyzing the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (AP-5) into the L7 or L6 and S1 levels of the dorsal horn of anesthetized cats. Contraction, elicited by electrical stimulation of the cut L7 and S1 ventral roots, increased mean arterial pressure (MAP) and heart rate (HR). Passive stretch at tensions similar to those generated by contraction also increased these variables. These cardiovascular changes were unaffected by dialyzing AP-5 (10 mM) into the dorsal horn at L7. Increasing the syringe concentration of AP-5 to 100 mM attenuated the pressor and HR responses from 62 +/- 8 to 31 +/- 6 mmHg and 18 +/- 4 to 12 +/- 4 beats/min, respectively. AP-5 blunted the increase in MAP (59 +/- 10 vs. 41 +/- 10 mmHg) evoked by muscle stretch. Simultaneously microdialyzing AP-5 (10 or 100 mM) into the dorsal horn at the L6 and S1 spinal levels also blunted the MAP and HR responses to contraction and stretch. These results suggest that NMDA receptors play a role in mediating the MAP and HR responses to static muscle contraction at the spinal level of the central nervous system. Furthermore, these data demonstrate that collaterals from muscle afferents partially mediate the reflex cardiovascular responses evoked by muscle contraction and stretch.

Reflex cardiovascular responses evoked by selective activation of skeletal muscle ergoreceptors

2001 ◽  
Vol 90 (1) ◽  
pp. 308-316 ◽  
Author(s):  
B. G. Leshnower ◽  
J. T. Potts ◽  
M. G. Garry ◽  
J. H. Mitchell
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Cardiovascular Response ◽  
Afferent Fiber ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Muscle Stretch ◽  
Group Iii ◽  
Passive Muscle

It is well known that the exercise pressor reflex (EPR) is mediated by group III and IV skeletal muscle afferent fibers, which exhibit unique discharge responses to mechanical and chemical stimuli. Based on the difference in discharge patterns of group III and IV muscle afferents, we hypothesized that activation of mechanically sensitive (MS) fibers would evoke a different pattern of cardiovascular responses compared with activation of both MS and chemosensitive (CS) fibers. Experiments were conducted in chloralose-urethane-anesthetized cats ( n = 10). Passive muscle stretch was used to activate MS afferents, and electrically evoked contraction of the triceps surae was used to activate both MS and CS muscle afferents. No significant differences were shown in reflex heart rate and mean arterial pressure (MAP) responses between passive muscle stretch and evoked muscle contraction. However, when the reflex responses were matched according to tension-time index (TTI), the peak MAP response (67 ± 4 vs. 56 ± 4 mmHg, P < 0.05) was significantly greater at higher TTI (427 ± 18 vs. 304 ± 13 kg · s, high vs. low TTI, P < 0.05), despite different modes of afferent fiber activation. When the same mode of afferent fiber activation was compared, the peak MAP response (65 ± 7 vs. 55 ± 5 mmHg, P < 0.05) was again predicted by the magnitude of TTI (422 ± 24 vs. 298 ± 19 kg · s, high vs. low TTI, P < 0.05). Total sensory input from skeletal muscle ergoreceptors, as predicted by TTI and not the modality of afferent fiber activation (muscle contraction vs. passive stretch), is suggested to be the primary determinant of the magnitude of the EPR-evoked cardiovascular response.

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 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 Blockade of the TP receptor attenuates the exercise pressor reflex in decerebrated rats with chronic femoral artery occlusion

2011 ◽  
Vol 301 (5) ◽  
pp. H2140-H2146 ◽  
Author(s):  
Anna K. Leal ◽  
Jennifer L. McCord ◽  
Hirotsugu Tsuchimochi ◽  
Marc P. Kaufman
Keyword(s):  
Peripheral Artery Disease ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Tp Receptor ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Artery Disease

Cyclooxygenase metabolites stimulate or sensitize group III and IV muscle afferents, which comprise the sensory arm of the exercise pressor reflex. The thromboxane (TP) receptor binds several of these metabolites, whose concentrations in the muscle interstitium are increased by exercise under freely perfused conditions and even more so under ischemic conditions, which occur in peripheral artery disease. We showed that the exercise pressor reflex is greater in rats with simulated peripheral artery disease than in rats with freely perfused limbs. These findings prompted us to test the hypothesis that the TP receptor contributes to the exaggerated exercise pressor reflex occurring in a rat model of peripheral artery disease. We compared the cardiovascular responses to static contraction and stretch before and after femoral arterial injections of daltroban (80 μg), a TP receptor antagonist. We performed these experiments in decerebrate rats whose femoral arteries were ligated 72 h before the experiment (a model of simulated peripheral artery disease) and in control rats whose hindlimbs were freely perfused. Daltroban reduced the pressor response to static contraction in both freely perfused ( n = 6; before: Δ12 ± 2 mmHg, after: Δ6 ± 2 mmHg, P = 0.024) and 72-h-ligated rats ( n = 10; before: Δ25 ± 3 mmHg, after: Δ7 ± 4 mmHg, P = 0.001). Likewise, daltroban reduced the pressor response to stretch in the freely perfused group ( n = 9; before: Δ30 ± 3 mmHg, after: Δ17 ± 3 mmHg, P < 0.0001) and in the ligated group ( n = 11; before: Δ37 ± 5 mmHg, after: Δ23 ± 3 mmHg, P = 0.016). Intravenous injections of daltroban had no effect on the pressor response to contraction. We conclude that the TP receptor contributes to the pressor responses evoked by contraction and stretch in both freely perfused rats and rats with simulated peripheral artery disease.

c-Fos expression in the midbrain periaqueductal gray during static muscle contraction

2000 ◽  
Vol 279 (6) ◽  
pp. H2986-H2993 ◽  
Author(s):  
Jianhua Li ◽  
Jere H. Mitchell
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Neuronal Cells ◽  
Cardiovascular Responses ◽  
Periaqueductal Gray ◽  
Exercise Pressor Reflex ◽  
Arterial Blood ◽  
Static Contraction ◽  
Afferent Inputs ◽  
Pressor Reflex

The periaqueductal gray (PAG) of the midbrain is involved in the autonomic regulation of the cardiovascular system. The purpose of this study was to determine if static contraction of the skeletal muscle, which increases arterial blood pressure and heart rate, activates neuronal cells in the PAG by examining Fos-like immunoreactivity (FLI). Muscle contraction was induced by electrical stimulation of the L7 and S1 ventral roots of the spinal cord in anesthetized cats. An intravenous infusion of phenylephrine (PE) was used to selectively activate arterial baroreceptors. Extensive FLI was observed within the ventromedial region (VM) of the rostral PAG, the dorsolateral (DL), lateral (L), and ventrolateral (VL) regions of the middle and caudal PAG in barointact animals with muscle contractions, and in barointact animals with PE infusion. However, muscle contraction caused a lesser number of FLI in the VM region of the rostral PAG, the DL, L, and VL regions of the middle PAG and the L and VL regions of the caudal PAG after barodenervation compared with barointact animals. Additionally, the number of FLI in the DL and L regions of the middle PAG was greater in barodenervated animals with muscle contraction than in barodenervated control animals. Thus these results indicated that both muscle receptor and baroreceptor afferent inputs activate neuronal cells in regions of the PAG during muscle contraction. Furthermore, afferents from skeletal muscle activate neurons in specific regions of the PAG independent of arterial baroreceptor input. Therefore, neuronal cells in the PAG may play a role in determining the cardiovascular responses during the exercise pressor reflex.

scholarly journals PO-126 Inhibition of HIF-1α Alleviates Exaggerated Pressor Response Induced by Static Muscle Contraction in Rats with Peripheral Arterial Disease

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Jianhua Li ◽  
Jihong Xing
Keyword(s):  
Blood Pressure ◽  
Muscle Contraction ◽  
Optical Density ◽  
Femoral Artery ◽  
Pressor Response ◽  
Artery Occlusion ◽  
Reflex Response ◽  
Exercise Pressor Reflex ◽  
Femoral Artery Occlusion ◽  
Pressor Reflex

Objective Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor mediating adaptive responses to hypoxia and ischemia. A prior work showed that HIF-1α is increased in sensory nerves of rats with femoral artery occlusion. The present study was to examine if the reflex response of blood pressure induced by muscle contraction was altered after injection of HIF-1α inhibitor BAY 87-2243 (BAY87) into the arterial blood supply of the ischemic hindlimb muscles.  Methods A rat model of femoral artery ligation was used to study peripheral artery disease. Western blot analysis was employed to examine the protein levels of HIF-1α in the dorsal root ganglion (DRG) tissues. The exercise pressor reflex was evoked by static muscle contraction.  Results HIF-1α was increased in the DRG of occluded limbs (optical density: 0.89±0.13 in control vs. 1.5±0.05 in occlusion; P < 0.05, n=6 in each group). Arterial injection of BAY87 (0.2 mg/kg) inhibited expression of HIF-1α in the DRG of occluded limbs three hours following its injection (optical density: 1.02±0.09 in occluded limbs with BAY87 vs. 1.06±0.1 in control limbs; P > 0.05, n=5 in each group). In addition, muscle contraction evoked a greater increase in blood pressure in occluded rats. BAY87 attenuated the enhanced pressor response in occluded rats to a greater degree than in control rats. Conclusions Inhibition of HIF-1α alleviates exaggeration of the exercise pressor reflex in rats under ischemic circumstances of the hindlimbs induced by femoral artery occlusion.   

scholarly journals Role played by acid-sensitive ion channels in evoking the exercise pressor reflex

2008 ◽  
Vol 295 (4) ◽  
pp. H1720-H1725 ◽  
Author(s):  
Shawn G. Hayes ◽  
Jennifer L. McCord ◽  
Jon Rainier ◽  
Zhuqing Liu ◽  
Marc P. Kaufman
Keyword(s):  
Lactic Acid ◽  
Ion Channels ◽  
Sodium Channels ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Thin Fiber ◽  
Exercise Pressor Reflex ◽  
Pressor Responses ◽  
Pressor Reflex

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half ( P < 0.05) the pressor responses to both contraction and to lactic acid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.

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