Blockade of non-NMDA receptors attenuates reflex pressor response to static contraction

1994 ◽  
Vol 266 (5) ◽  
pp. H1769-H1776 ◽  
Author(s):  
J. M. Hill ◽  
J. G. Pickar ◽  
M. P. Kaufman
Keyword(s):  
Nmda Receptor ◽  
Substance P ◽  
Receptor Antagonist ◽  
Pressor Response ◽  
Intrathecal Injection ◽  
Ventilatory Responses ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Substance P Receptor ◽  
Pressor Reflex

Considerable evidence suggests that both substance P and glutamate play a role in the spinal transmission of the exercise pressor reflex. We tested two hypotheses. First, after a lumbosacral intrathecal injection of a glutamatergic receptor antagonist, the reflex cardiovascular and ventilatory responses to static contraction are attenuated. Second, after a lumbosacral intrathecal injection of a substance P receptor antagonist and a glutamatergic receptor antagonist, the reflex cardiovascular and ventilatory responses to static contraction are abolished. We found that 1) the reflex cardiovascular responses to static contraction were unaffected (P > 0.05) after the intrathecal injection of the N-methyl-D-aspartate (NMDA) receptor antagonists, dl-2-amino-5-phosphonopentanoate (+/- AP-5) or 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (+/- CPP); 2) the reflex pressor response to static muscular contraction was attenuated by > 50% after the intrathecal injection of the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); and 3) the reflex pressor response to static contraction was almost abolished after the intrathecal injection of the substance P receptor antagonist, CP-96,345, and CNQX. Our results suggest that substance P and glutamate are two neurotransmitters involved in the spinal transmission of the exercise pressor reflex and that substance P and glutamate exert their effects via neurokinin-1 (NK-1) and non-NMDA receptors, respectively.

Attenuation of reflex pressor and ventilatory responses to static contraction by an NK-1 receptor antagonist

1992 ◽  
Vol 73 (4) ◽  
pp. 1389-1395 ◽  
Author(s):  
J. M. Hill ◽  
J. G. Pickar ◽  
M. P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Receptor Antagonist ◽  
Dorsal Horn ◽  
Intrathecal Injection ◽  
Muscular Contraction ◽  
Muscle Afferents ◽  
Neurokinin A ◽  
Ventilatory Responses ◽  
Static Contraction

The chemical messengers released onto second-order dorsal horn neurons from the spinal terminals of contraction-activated group III and IV muscle afferents have not been identified. One candidate is the tachykinin substance P. Related to substance P are two other tachykinins, neurokinin A (NKA) and neurokinin B (NKB), which, like substance P, have been isolated in the dorsal horn of the spinal cord and have receptors there. Whether NKA or NKB plays a transmitter/modulator role in the spinal processing of the exercise pressor reflex is unknown. Therefore, we tested the following hypotheses. After the intrathecal injection of a highly selective NK-1 (substance P) receptor antagonist onto the lumbosacral spinal cord, the reflex pressor and ventilatory responses to static muscular contraction will be attenuated. Likewise, after the intrathecal injection either of an NK-2 (NKA) receptor antagonist or an NK-3 (NKB) receptor antagonist onto the lumbrosacral spinal cord, the reflex pressor and ventilatory responses to static contraction will be attenuated. We found that, 10 min after the intrathecal injection of 100 micrograms of the NK-1 receptor antagonist, the pressor and ventilatory responses to contraction were significantly (P < 0.05) attenuated. Mean arterial pressure was attenuated by 13 +/- 3 mmHg (48%) and minute volume of ventilation by 120 +/- 38 ml/min (34%). The cardiovascular and ventilatory responses to contraction before either 100 micrograms of the NK-2 receptor antagonist or 100 micrograms of the NK-3 receptor antagonist were not different (P > 0.05) from those after the NK-2 or the NK-3 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

scholarly journals Glutamatergic receptor dysfunction in spinal cord contributes to the exaggerated exercise pressor reflex in heart failure

2015 ◽  
Vol 308 (5) ◽  
pp. H447-H455 ◽  
Author(s):  
Han-Jun Wang ◽  
Rebecca Cahoon ◽  
Edgar B. Cahoon ◽  
Hong Zheng ◽  
Kaushik P. Patel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Spinal Cord ◽  
Receptor Antagonist ◽  
Dorsal Horn ◽  
Pressor Response ◽  
Glutamate Release ◽  
Exercise Pressor Reflex ◽  
Dorsal Horns ◽  
Static Contraction ◽  
Pressor Reflex

Excitatory amino acids (e.g., glutamate) released by contraction-activated skeletal muscle afferents into the dorsal horn of the spinal cord initiate the central component of the exercise pressor reflex (EPR) in physiological conditions. However, the role of glutamate and glutamate receptors in mediating the exaggerated EPR in the chronic heart failure (CHF) state remains to be determined. In the present study, we performed microinjection of glutamate receptor antagonists into ipisilateral L4/L5 dorsal horns to investigate their effects on the pressor response to static contraction induced by stimulation of the peripheral end of L4/L5 ventral roots in decerebrate sham-operated (sham) and CHF rats. Microinjection of glutamate (10 mM, 100 nl) into the L4 or L5 dorsal horn caused a greater pressor response in CHF rats compared with sham rats. Furthermore, microinjection of either the broad-spectrum glutamate receptor antagonist kynurenate (10 mM, 100 nl) or the N-methyl-d-aspartate (NMDA) receptor antagonist dl-2-amino-5-phosphonovalerate (50 mM, 100 nl) or the non-NMDA-sensitive receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (5 mM, 100 nl) into L4/5 dorsal horns decreased the pressor response to static contraction in CHF rats to a greater extent than in sham rats. Molecular evidence showed that the protein expression of glutamate receptors (both non-NMDA and NMDA) was elevated in the dorsal horn of the lumbar spinal cord in CHF rats. In addition, data from microdialysis experiments demonstrated that although basal glutamate release at the dorsal horn at rest was similar between sham and CHF rats (225 ± 50 vs. 260 ± 63 nM in sham vs. CHF rats, n = 4, P > 0.05), CHF rats exhibit greater glutamate release into the dorsal horn during muscle contraction compared with sham rats (549 ± 60 vs. 980 ± 65 nM in sham vs. CHF rats, n = 4, P < 0.01). These data indicate that the spinal glutamate system contributes to the exaggerated EPR in the CHF state.

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.

Estrogen attenuates the cardiovascular and ventilatory responses to central command in cats

2002 ◽  
Vol 92 (4) ◽  
pp. 1635-1641 ◽  
Author(s):  
Shawn G. Hayes ◽  
Nicolas B. Moya Del Pino ◽  
Marc P. Kaufman
Keyword(s):  
Triceps Surae ◽  
Central Command ◽  
Neuronal Function ◽  
Ventilatory Responses ◽  
Exercise Pressor Reflex ◽  
Arterial Blood ◽  
Static Contraction ◽  
17Β Estradiol ◽  
Pressor Reflex ◽  
Triceps Surae Muscles

Static exercise is well known to increase heart rate, arterial blood pressure, and ventilation. These increases appear to be less in women than in men, a difference that has been attributed to an effect of estrogen on neuronal function. In decerebrate male cats, we examined the effect of estrogen (17β-estradiol; 0.001, 0.01, 0.1, and 1.0 μg/kg iv) on the cardiovascular and ventilatory responses to central command and the exercise pressor reflex, the two neural mechanisms responsible for evoking the autonomic and ventilatory responses to exercise. We found that 17β-estradiol, in each of the three doses tested, attenuated the pressor, cardioaccelerator, and phrenic nerve responses to electrical stimulation of the mesencephalic locomotor region (i.e., central command). In contrast, none of the doses of 17β-estradiol had any effect on the pressor, cardioaccelerator, and ventilatory responses to static contraction or stretch of the triceps surae muscles. We conclude that, in decerebrate male cats, estrogen injected intravenously attenuates cardiovascular and ventilatory responses to central command but has no effect on responses to the exercise pressor reflex.

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.

Augmentation of the exercise pressor reflex in prehypertension: roles of the muscle metaboreflex and mechanoreflex

2013 ◽  
Vol 38 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Hyun-Min Choi ◽  
Charles L. Stebbins ◽  
Og-Taeg Lee ◽  
Hosung Nho ◽  
Joon-Hee Lee ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Response ◽  
Pressor Response ◽  
Peripheral Resistance ◽  
Percentage Increase ◽  
Muscle Metaboreflex ◽  
Exercise Pressor Reflex ◽  
Arterial Blood ◽  
Static Contraction ◽  
Pressor Reflex

This study investigated the hemodynamic mechanisms underlying the exaggerated blood pressure response to muscle contraction in prehypertensive humans and the potential role of skeletal muscle metabo- and mechanoreceptors in this response. To accomplish this, changes in peak mean arterial blood pressure (ΔMAP), cardiac output, and total peripheral resistance (ΔTPR) were compared between prehypertensive (n = 23) and normotensive (n = 19) male subjects during 2 min of static contraction (at 50% of maximal tension), 2 min of postexercise muscle ischemia (metaboreflex), and 1 min of passive dorsiflexion of the foot (tendon stretch, mechanoreceptor reflex). These variables were assessed before and during the interventions. Percentage increases from baseline in MAP and TPR in response to the exercise pressor reflex were augmented in the prehypertensives, compared with the normotensives (44% ± 5% vs. 33% ± 4% and 34% ± 15% vs. 2% ± 8%, respectively) (p < 0.05). Metaboreflex-induced increases in MAP and TPR were also augmented in the prehypertensives (28% ± 5% vs. 14% ± 4% and 36% ± 12% vs. 14% ± 9%, respectively) (p < 0.05). In response to the mechanoreflex, no differences in the percentage increase in MAP or TPR were seen between groups. The results indicate that the reflex pressor response to static contraction is augmented in prehypertension and suggest that this phenomenon is due, at least in part, to enhanced activation of metaboreceptors.

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