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.

Vanilloid type 1 receptor and the acid-sensing ion channel mediate acid phosphate activation of muscle afferent nerves in rats

2006 ◽  
Vol 100 (2) ◽  
pp. 421-426 ◽  
Author(s):  
Zhaohui Gao ◽  
Oze Henig ◽  
Valerie Kehoe ◽  
Lawrence I. Sinoway ◽  
Jianhua Li
Keyword(s):  
Purinergic Receptor ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
Reflex Response ◽  
Disulfonic Acid ◽  
Thin Fiber ◽  
Arterial Blood ◽  
Afferent Nerves ◽  
Muscle Afferent

Reflex cardiovascular responses to contracting skeletal muscle are mediated by mechanical and metabolic stimulation of thin-fiber muscle afferents. Diprotonated phosphate (H2PO4−) excites those thin-fiber nerves and evokes the muscle pressor reflex. The receptors mediating this response are unknown. Thus we examined the role played by purinergic receptors, vanilloid type 1 receptors (VR1), and acid-sensing ion channels (ASIC) in mediating H2PO4−-evoked pressor responses. Phosphate and blocking agents were injected into the arterial blood supply of the hindlimb muscles of 53 decerebrated rats. H2PO4− (86 mM, pH 6.0) increased mean arterial pressure by 25 ± 2 mmHg, whereas monoprotonated phosphate (HPO42−, pH 7.5) had no effect. Pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (a purinergic receptor antagonist, 2 mM) did not block the response. However, capsazepine (a VR1 antagonist, 1 mg/kg) attenuated the reflex by 60% and amiloride (an ASIC blocker, 6 μg/kg) by 52%. Of note, the H2PO4−-induced pressor response was attenuated by 87% when both capsazepine and amiloride were injected before the H2PO4−. In conclusion, VR1 and ASIC mediate the pressor response due to H2PO4−. The H2PO4−-evoked response was greater when VR1 and ASIC blockers were given simultaneously than when the respective blockers were given separately. Our laboratory's previous study has shown that H+ stimulates ASIC (but not VR1) on thin-fiber afferent nerves in evoking the reflex response. Thus VR1 and ASIC are likely to play a coordinated and interactive role in processing the muscle afferent response to H2PO4−. Furthermore, the physiological mechanisms mediating the response to H+ and H2PO4− are likely to be different.

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.

Bradykinin BK2 receptors contribute to reflex cardiovascular responses during brief abdominal ischemia

1998 ◽  
Vol 274 (1) ◽  
pp. H308-H313 ◽  
Author(s):  
Premjit S. Chahal ◽  
Stephen V. Rendig ◽  
John C. Longhurst
Keyword(s):  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
Nerve Fibers ◽  
Reflex Response ◽  
Receptor Antagonists ◽  
Artery Ligation ◽  
Sympathetic Nerve Fibers ◽  
Arterial Blood ◽  
Afferent Nerves ◽  
Hoe 140

Ischemically sensitive visceral sympathetic nerve fibers, which are thought to represent the afferent limb of a strong cardiovascular pressor reflex, can be stimulated by exogenously applied bradykinin (BK). During ischemia, BK also is known to be produced locally and to serve as an endogenous stimulus for activation of ischemically sensitive nerve endings. It is unclear, however, whether ischemically induced BK production is sufficient to elicit a reflex cardiovascular response. Accordingly, femoral arterial and venous catheters were positioned in anesthetized cats, and the superior mesenteric and celiac arteries were isolated for placement of snare occluders. After dual occlusion of these arteries (20 min), one of two chemically dissimilar specific kinin B2(BK2) receptor antagonists, HOE-140 (30–40 μg/kg iv, n = 8) or NPC-17731 (30–40 μg/kg iv, n= 11), was administered and dual occlusion was repeated. The reflex rise of mean arterial blood pressure (BP) of 16 ± 3.7% was significantly ( P < 0.05) reduced by HOE-140 to 8.4 ± 2.0%. NPC-17731 similarly attenuated the reflex BP increment from 13 ± 1.2 to 6.2 ± 1.6% ( P < 0.05). In a separate set of control animals the first and second periods of ischemia induced reflex BP increments that did not differ significantly (16 ± 2.7 and 16 ± 5.7%, respectively). Qualitatively similar decrements of the BP response were produced by the BK2 receptor antagonists in two additional groups in which blood flow to the superior mesenteric and celiac arteries was diverted to a venous reservoir to eliminate the initial transient (mechanically induced) rise in BP associated with artery ligation that is known not to be associated with the reflex response. These results indicate that the stimulation of BK2 receptors on visceral afferent nerves by BK is responsible, at least in part, for the reflex cardiovascular response during visceral ischemia.

Temperature modulates P2X receptor-mediated cardiovascular responses to muscle afferent activation

2006 ◽  
Vol 291 (3) ◽  
pp. H1255-H1261 ◽  
Author(s):  
Zhaohui Gao ◽  
Valerie Kehoe ◽  
Jihong Xing ◽  
Lawrence Sinoway ◽  
Jianhua Li
Keyword(s):  
Muscle Contraction ◽  
Atp Release ◽  
Cardiovascular Responses ◽  
P2x Receptors ◽  
Muscle Afferents ◽  
P2x Receptor ◽  
Muscle Temperature ◽  
Muscle Stretch ◽  
Arterial Blood ◽  
Muscle Afferent

Static muscle contraction increases ATP release into the muscle interstitial space. Elevated ATP in muscle stimulates thin fiber muscle afferents and increases blood pressure via engagement of purinergic P2X receptors. In addition, ATP activates P2X receptors and enhances cardiovascular responses induced by stimulation of muscle mechanoreceptors. In this study, we examined whether elevated muscle temperature would attenuate and whether reduced temperature would potentiate P2X effects on reflex muscle responses. α,β-Methylene ATP (α,β-MeATP) was injected into the arterial blood supply of hindlimb muscle to stimulate P2X receptors, and muscle stretch was induced to activate mechanically sensitive muscle afferents as α,β-MeATP was injected in 10 anesthetized cats. Femoral arterial injection of α,β-MeATP (1.0 mM) increased mean arterial pressure (MAP) by 35 ± 5 (35°C), 26 ± 3 (37°C), and 19 ± 3 mmHg (39°C; P < 0.05 vs. 35°C), respectively. Muscle stretch (2 kg) elevated MAP. The MAP response was significantly enhanced 34% and 36% when α,β-MeATP (0.2 mM) was arterially infused 5 min before muscle stretch at 35° and 37°C, respectively. However, as muscle temperature reached 39°C, the stretch-evoked response was augmented only 6% by α,β-MeATP injection, and the response was significantly attenuated compared with the response with muscle temperature of 35° and 37°C. In addition, we also examined effects of muscle temperature on α,β-MeATP enhancement of the cardiovascular responses to static muscle contraction while the muscles were freely perfused and the circulation to the muscles was occluded. Because muscle temperature was 37°C, arterial injections of α,β-MeATP significantly augmented contraction-evoked MAP response by 49% (freely perfused) and 53% (ischemic condition), respectively. It is noted that this effect was significantly attenuated at a muscle temperature of 39°C. These data indicate that the effect of P2X receptor on reflex muscle response is sensitive to alternations of muscle temperature and that elevated temperature attenuates the response.

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.

Spinal P2X receptor modulates reflex pressor response to activation of muscle afferents

2005 ◽  
Vol 288 (5) ◽  
pp. H2238-H2243 ◽  
Author(s):  
Zhaohui Gao ◽  
Valerie Kehoe ◽  
Lawrence I. Sinoway ◽  
Jianhua Li
Keyword(s):  
Dorsal Horn ◽  
Pressor Response ◽  
Cardiovascular Responses ◽  
P2x Receptors ◽  
Muscle Afferents ◽  
P2x Receptor ◽  
Reflex Response ◽  
Disulfonic Acid ◽  
Synaptic Site ◽  
Stimulation Of

Static contraction of skeletal muscle evokes increases in blood pressure and heart rate. Previous studies suggested that the dorsal horn of the spinal cord is the first synaptic site responsible for those cardiovascular responses. In this study, we examined the role of ATP-sensitive P2X receptors in the cardiovascular responses to contraction by microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) into the L7 level of the dorsal horn of nine anesthetized cats. Contraction was elicited by electrical stimulation of the L7 and S1 ventral roots. Blockade of P2X receptor attenuated the contraction induced-pressor response [change in mean arterial pressure (ΔMAP): 16 ± 4 mmHg after 10 mM PPADS vs. 42 ± 8 mmHg in control; P < 0.05]. In addition, the pressor response to muscle stretch was also blunted by PPADS (ΔMAP: 27 ± 5 mmHg after PPADS vs. 49 ± 8 mmHg in control; P < 0.05). Finally, activation of P2X receptor by microdialyzing 0.5 mM α,β-methylene into the dorsal horn significantly augmented the pressor response to contraction. This effect was antagonized by prior PPADS dialysis. These data demonstrate that blockade of P2X receptors in the dorsal horn attenuates the pressor response to activation of muscle afferents and that stimulation of P2X receptors enhances the reflex response, indicating that P2X receptors play a role in mediating the muscle pressor reflex at the first synaptic site of this reflex.

scholarly journals Role for NGF in augmented sympathetic nerve response to activation of mechanically and metabolically sensitive muscle afferents in rats with femoral artery occlusion

2012 ◽  
Vol 113 (8) ◽  
pp. 1311-1322 ◽  
Author(s):  
Jian Lu ◽  
Jihong Xing ◽  
Jianhua Li
Keyword(s):  
Blood Pressure ◽  
Lactic Acid ◽  
Drg Neurons ◽  
Hindlimb Muscles ◽  
Arterial Blood ◽  
Afferent Nerves ◽  
Static Contraction ◽  
C Fiber ◽  
Muscle Afferent ◽  
Stimulation Of

Arterial blood pressure and heart rate responses to static contraction of the hindlimb muscles are greater in rats whose femoral arteries were previously ligated than in control rats. Also, the prior findings demonstrate that nerve growth factor (NGF) is increased in sensory neurons-dorsal root ganglion (DRG) neurons of occluded rats. However, the role for endogenous NGF in engagement of the augmented sympathetic and pressor responses to stimulation of mechanically and/or metabolically sensitive muscle afferent nerves during static contraction after femoral artery ligation has not been specifically determined. In the present study, both afferent nerves and either of them were activated by muscle contraction, passive tendon stretch, and arterial injection of lactic acid into the hindlimb muscles. Data showed that femoral occlusion-augmented blood pressure response to contraction was significantly attenuated by a prior administration of the NGF antibody (NGF-Ab) into the hindlimb muscles. The effects of NGF neutralization were not seen when the sympathetic nerve and pressor responses were evoked by stimulation of mechanically sensitive muscle afferent nerves with tendon stretch in occluded rats. In addition, chemically sensitive muscle afferent nerves were stimulated by lactic acid injected into arterial blood supply of the hindlimb muscles after the prior NGF-Ab, demonstrating that the reflex muscle responses to lactic acid were significantly attenuated. The results of this study further showed that NGF-Ab attenuated an increase in acid-sensing ion channel subtype 3 (ASIC3) of DRG in occluded rats. Moreover, immunohistochemistry was employed to examine the number of C-fiber and A-fiber DRG neurons. The data showed that distribution of DRG neurons with different thin fiber phenotypes was not notably altered when NGF was infused into the hindlimb muscles. However, NGF increased expression of ASIC3 in DRG neurons with C-fiber but not A-fiber. Overall, these data suggest that 1) NGF is amplified in sensory nerves of occluded rats and contributes to augmented reflex sympathetic and blood pressure responses evoked by stimulation of chemically, but not mechanically, sensitive muscle afferent nerves and 2) NGF likely plays a role in modulating the muscle metaboreflex via enhancement of ASIC3 expression in C-fiber of DRG neurons.

scholarly journals Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

2016 ◽  
Vol 39 (6) ◽  
pp. 2101-2109 ◽  
Author(s):  
Jihong Xing ◽  
Jianhua Li
Keyword(s):  
Heart Failure ◽  
Nervous Activity ◽  
Muscle Afferents ◽  
Receptor Expression ◽  
Sympathetic Nervous Activity ◽  
Published Data ◽  
Drg Neurons ◽  
Arterial Blood ◽  
Pressor Responses ◽  
Muscle Afferent

Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA) and blood pressure (BP) responses during static exercise in heart failure (HF). In this study, we examined engagement of bradykinin (BK) in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG) neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.

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.

Interactions between brain acetylcholine and prostaglandins in control of vasopressin release

1991 ◽  
Vol 261 (2) ◽  
pp. R420-R426
Author(s):  
M. Inoue ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Cardiovascular Responses ◽  
Vasopressin Release ◽  
Arterial Blood ◽  
Plasma Vasopressin ◽  
Vasopressin Secretion ◽  
Stimulation Of

We have examined in conscious rats the interaction between centrally acting prostanoids and acetylcholine in the stimulation of vasopressin secretion. The intracerebroventricular (icv) administration of carbachol (25 ng) resulted in marked transient increases in the plasma vasopressin concentration and mean arterial blood pressure and a transient reduction in heart rate. Central cyclooxygenase blockade by pretreatment icv with either meclofenamate (100 micrograms) or indomethacin (100 micrograms) virtually completely blocked these responses. Prostaglandin (PG) D2 (20 micrograms icv) caused transient increases in the plasma vasopressin concentration (much smaller than after carbachol) and heart rate, whereas mean arterial blood pressure rose gradually during the 15-min course of the experiment. Pretreatment with the muscarinic antagonist atropine (10 micrograms icv) decreased the peak vasopressin response to icv PGD2 by approximately one-third but had no effect on the cardiovascular responses. We conclude that the stimulation of vasopressin release by centrally acting acetylcholine is dependent on increased prostanoid biosynthesis. On the other hand, stimulation of vasopressin release by icv PGD2 is partially dependent on activation of a cholinergic pathway.

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