Midbrain vlPAG inhibits rVLM cardiovascular sympathoexcitatory responses during electroacupuncture

2006 ◽  
Vol 290 (6) ◽  
pp. H2543-H2553 ◽  
Author(s):  
Stephanie C. Tjen-A-Looi ◽  
Peng Li ◽  
John C. Longhurst
Keyword(s):  
Blood Pressure ◽  
Excitatory Amino Acid ◽  
Sympathetic Neurons ◽  
Cardiovascular Responses ◽  
Splanchnic Nerve ◽  
Ventrolateral Medulla ◽  
Inhibitory Influence ◽  
Afferent Stimulation ◽  
Homocysteic Acid ◽  
Blood Pressure Responses

The periaqueductal gray (PAG) is an important integrative region in the regulation of autonomic outflow and cardiovascular function and may serve as a regulatory center as part of a long-loop pathway during somatic afferent stimulation with acupuncture. Because the ventrolateral PAG (vlPAG) provides input to the rostral ventrolateral medulla (rVLM), an important area for electroacupuncture (EA) regulation of sympathetic outflow, we hypothesized that the vlPAG plays a role in the EA-related modulation of rVLM premotor sympathetic neurons activated during visceral afferent stimulation and autonomic excitatory reflexes. Cats were anesthetized and ventilated, and heart rate and mean blood pressure were monitored. Stimulation of the splanchnic nerve by a pledget of filter paper soaked in bradykinin (BK, 10 μg/ml) every 10 min on the gallbladder induced consistent cardiovascular reflex responses. Bilateral stimulation with EA at acupoints over the pericardial meridian (P5-6) situated over the median nerve reduced the increases in blood pressure from 34 ± 3 to 18 ± 5 mmHg for a period of time that lasted for 60 min or more. Unilateral inactivation of neuronal activity in the vlPAG with 50–75 nl of kainic acid (KA, 1 mM) restored the blood pressure responses from 18 ± 3 to 36 ± 5 mmHg during BK-induced gallbladder stimulation, an effect that lasted for 30 min. In the absence of EA, unilateral microinjection of the excitatory amino acid dl-homocysteic acid (DLH, 4 nM) in the vlPAG mimicked the effect of EA and reduced the reflex blood pressure responses from 35 ± 6 to 14 ± 5 mmHg. Responses of 21 cardiovascular sympathoexcitatory rVLM neurons, including 12 that were identified as premotor neurons, paralleled the cardiovascular responses. Thus splanchnic nerve-evoked neuronal discharge of 32 ± 4 spikes/30 stimuli in six neurons was reduced to 10 ± 2 spikes/30 stimuli by EA, which was restored rapidly to 28 ± 4 spikes/30 stimuli by unilateral injection of 50 nl KA into the vlPAG. Conversely, 50 nl of DLH in the vlPAG reduced the number of action potentials of 5 rVLM neurons from 30 ± 4 to 18 ± 4 spikes/30 stimuli. We conclude that the inhibitory influence of EA involves vlPAG stimulation, which, in turn, inhibits rVLM neurons in the EA-related attenuation of the cardiovascular excitatory response during visceral afferent stimulation.

Excitatory projections from arcuate nucleus to ventrolateral periaqueductal gray in electroacupuncture inhibition of cardiovascular reflexes

2006 ◽  
Vol 290 (6) ◽  
pp. H2535-H2542 ◽  
Author(s):  
Peng Li ◽  
Stephanie C. Tjen-A-Looi ◽  
John C. Longhurst
Keyword(s):  
Arcuate Nucleus ◽  
Excitatory Amino Acid ◽  
Splanchnic Nerve ◽  
Periaqueductal Gray ◽  
Ventrolateral Medulla ◽  
Cardiovascular Reflexes ◽  
Inhibitory Influence ◽  
Homocysteic Acid ◽  
Electrophysiological Recordings ◽  
Stimulation Of

We have shown that the modulatory effect of electroacupuncture (EA) on the blood pressure (BP) response induced by visceral organ stimulation is related to inhibition of cardiovascular neurons in the rostral ventrolateral medulla (rVLM) through a mechanism that involves opioids. This effect is long lasting and may involve a long-loop neural supraspinal pathway, including the arcuate nucleus (ARC), which is an important site of opioid neurotransmitter synthesis. Therefore, we evaluated the role of the hypothalamic ARC and its interaction with the midbrain ventrolateral periaqueductal gray (vlPAG) in the EA-BP response. The gallbladder of α-chloralose-anesthetized cats was stimulated to test for the influence of EA on splanchnic afferent-induced cardiovascular reflexes. Electrodes were placed around the splanchnic nerve (SN), and acupuncture needles were applied at P5-6 acupoints overlying the median nerve (MN). Electrophysiological recordings showed that spontaneous activity of ARC and vlPAG neurons was low (1.3 ± 0.5 and 2.0 ± 0.5 spikes/s, respectively). We observed a gradation of responses of ARC neurons to the stimulation of different acupoints, ranging from uniform responses of all neurons during stimulation of the P5-6, LI4-11, H5-6, and St2-G2 located over deep nerves to fewer responses during stimulation of LI6-7 and G37-39 located over superficial nerves. Microinjection of the excitatory amino acid dl-homocysteic acid (DLH 4 nM, 50 nl) into the ARC augmented the responses of vlPAG neurons, whereas microinjection of kainic acid (KA 1 mM, 50 nl) to deactivate neurons in the ARC decreased vlPAG responses to SN stimulation. Thirty minutes of EA at P5-6 increased the SN-evoked discharge of vlPAG neurons (7.0 ± 1.2 to 14.3 ± 3.0 spikes/30 stimuli), a response that was blocked by microinjection of KA into the ARC. Microinjection of DLH into the ARC, like EA, inhibited (30 min) the reflex increase in BP induced by application of bradykinin (BK) to the gallbladder, whereas microinjection of KA into the ARC blocked the inhibitory influence of EA at P5-6 on the BK-induced BP response. These results suggest that excitatory projections from the ARC to the vlPAG are essential to the EA inhibition of the reflex increase in BP induced by SN or gallbladder visceral afferent stimulation.

Differential cardiorespiratory control elicited by activation of ventral medullary sites in mice

2000 ◽  
Vol 89 (2) ◽  
pp. 437-444 ◽  
Author(s):  
F. P. Tolentino-Silva ◽  
M. A. Haxhiu ◽  
P. Ernsberger ◽  
S. Waldbaum ◽  
I. A. Dreshaj
Keyword(s):  
Blood Pressure ◽  
Adrenergic Receptors ◽  
Excitatory Amino Acid ◽  
Signal Transduction Pathway ◽  
Ventrolateral Medulla ◽  
Respiratory Drive ◽  
Breathing Frequency ◽  
Cardiorespiratory Control ◽  
Blood Pressure Responses ◽  
Stimulation Of

We studied the respiratory and blood pressure responses to chemical stimulation of two regions of the ventral brainstem in mice: the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). Stimulation of the RVLM by microinjections of the excitatory amino acid l-glutamate induced increases in diaphragm activity and breathing frequency, elevation of blood pressure (BP), and a slight increase in heart rate (HR). However, activation of the CVLM induced a decrease in breathing frequency, mainly due to prolongation of expiratory time (Te), and hypotension associated with a slight slowing of HR. Because adrenergic mechanisms are known to participate in the control of respiratory timing, we examined the role of α2-adrenergic receptors in the RVLM region in mediating these inhibitory effects. The findings demonstrated that blockade of the α2-adrenergic receptors within the RVLM by prior microinjection of SKF-86466 (an α2-adrenergic receptor blocker) significantly reduced changes in Te induced by CVLM stimulation but had little effect on BP responses. These results indicate that, in mice, activation of the RVLM increases respiratory drive associated with an elevation of BP, but stimulation of CVLM induces prolongation of Te via an α2-adrenergic signal transduction pathway.

Inhibition of baroreflex vagal bradycardia by activation of the rostral ventrolateral medulla in rats

2000 ◽  
Vol 279 (3) ◽  
pp. H1239-H1247 ◽  
Author(s):  
Shoichiro Nosaka ◽  
Keiko Murata ◽  
Masayoshi Kobayashi ◽  
Zhi Bin Cheng ◽  
Junko Maruyama
Keyword(s):  
Blood Pressure ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Inhibitory Influence ◽  
Homocysteic Acid ◽  
Aortic Depressor Nerve ◽  
Inspiratory Activity ◽  
Gaba Antagonist ◽  
Vagal Bradycardia

In stressful conditions, baroreflex vagal bradycardia (BVB) is often suppressed while blood pressure is increased. To address the role of the rostral ventrolateral medulla (RVL), a principal source of sympathetic tone, in inhibition of BVB, we microinjected dl-homocysteic acid (DLH, 6 nmol) into the RVL of chloralose-urethan-anesthetized, sinoaortic-denervated rats to examine the effect on BVB. The BVB was provoked by electrical stimulation of the aortic depressor nerve ipsilateral to the injection sites. DLH microinjection was found to suppress BVB while increasing blood pressure. The inhibition of BVB was observed even during the early phase in which DLH transiently suppressed central inspiratory activity. The inhibition was not affected either by upper spinal cord transection or suprapontine decerebration. Similar results were obtained by microinjection of bicuculline methiodide (160 pmol), a GABA antagonist, into the RVL of carotid sinus nerve-preserved rats due to withdrawal of a tonic GABA-mediated, inhibitory influence including the input from arterial baroreceptors. In conclusion, activation of the RVL inhibits BVB at brain stem level independently of central inspiratory drive.

scholarly journals Nucleus raphé pallidus participates in midbrain-medullary cardiovascular sympathoinhibition during electroacupuncture

2010 ◽  
Vol 299 (5) ◽  
pp. R1369-R1376 ◽  
Author(s):  
Peng Li ◽  
Stephanie C. Tjen-A-Looi ◽  
John C. Longhurst
Keyword(s):  
Blood Pressure ◽  
Kynurenic Acid ◽  
Arcuate Nucleus ◽  
Neuronal Response ◽  
Splanchnic Nerve ◽  
Ventrolateral Medulla ◽  
Recording Electrode ◽  
Indirect Pathway ◽  
Homocysteic Acid ◽  
Raphe Pallidus

We have shown that electroacupuncture (EA) inhibits sympathoexcitatory rostral ventrolateral medulla (rVLM) neurons and reflex responses following activation of a long-loop pathway in the arcuate nucleus and ventrolateral periaqueductal gray (vlPAG). Additionally, EA at P 5–6 acupoints (overlying the median nerve) activates serotonin-containing neurons in the nucleus raphé pallidus (NRP), which, in turn, inhibit rVLM neurons. Although direct projections from the vlPAG to the rVLM exist, it is uncertain whether an indirect pathway through the NRP serves an important role in vlPAG-rVLM cardiovascular modulation. Therefore, the splanchnic nerve (SN) was stimulated to induce cardiovascular sympathoexcitatory reflexes, and EA was applied at P 5–6 acupoints in α-chloralose-anesthetized cats. A single-barreled recording electrode was inserted into the NRP or rVLM. Microinjection of dl-homocysteic acid (DLH) into the vlPAG increased the NRP neuronal response to SN stimulation (5 ± 1 to 12 ± 2 spikes/30 stim). Likewise, EA at P 5–6 for 30 min increased the NRP response to SN stimulation (3 ± 1 to 10 ± 2 spikes/30 stim), an effect that could be blocked by microinjection of kynurenic acid (KYN) into the caudal vlPAG. Furthermore, the reflex increase in blood pressure induced by application of bradykinin to the gallbladder and the rVLM cardiovascular presympathetic neuronal response to SN stimulation was inhibited by injection of DLH into the vlPAG, a response that was reversed by injection of KYN into the NRP. These results indicate that EA activates the vlPAG, which excites the NRP to, in turn, inhibit rVLM presympathetic neurons and reflex cardiovascular sympathoexcitatory responses.

Cardiac baroreflex facilitation evoked by hypothalamus and prefrontal cortex stimulation: role of the nucleus tractus solitarius 5-HT2A receptors

2006 ◽  
Vol 291 (4) ◽  
pp. R1007-R1015 ◽  
Author(s):  
C. Sévoz-Couche ◽  
M. A. Comet ◽  
J. F. Bernard ◽  
M. Hamon ◽  
R. Laguzzi
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Prefrontal Cortex ◽  
Nucleus Tractus Solitarius ◽  
Cardiovascular Responses ◽  
Receptor Activation ◽  
Cardiac Response ◽  
Inhibitory Influence ◽  
Homocysteic Acid

We previously showed that serotonin (5-HT2) receptor activation in the nucleus of the tractus solitarius (NTS) produced hypotension, bradycardia, and facilitation of the baroreflex bradycardia. Activation of the preoptic area (POA) of the hypothalamus, which is involved in shock-evoked passive behaviors, induces similar modifications. In addition, previous studies showed that blockade of the infralimbic (IL) part of the medial prefrontal cortex, which sends projections to POA, produced an inhibitory influence on the baroreflex cardiac response. Thus, to assess the possible implication of NTS 5-HT2 receptors in passive cardiovascular responses, we analyzed in anesthetized rats the effects of NTS inhibition and NTS 5-HT2 receptor blockade on the cardiovascular modifications induced by chemical (0.3 M d,l-homocysteic acid) and electrical (50 Hz, 150–200 μA) stimulation of IL or POA. Intra-NTS microinjections of muscimol, a GABAA receptor agonist, prevented the decreases in blood pressure and heart rate normally evoked by IL or POA activation. In addition, we found that intra-NTS microinjection of R(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol, a specific 5-HT2A receptor antagonist, did not affect the decreases in cardiovascular baseline parameters induced by IL or POA stimulation but prevented the facilitation of the aortic baroreflex bradycardia normally observed during IL (+65 and +60%) or POA (+70 and +69%) electrical and chemical stimulation, respectively. These results show that NTS 5-HT2A receptors play a key role in the enhancement of the cardiac response of the baroreflex but not in the changes in basal heart rate and blood pressure induced by IL or POA stimulation.

scholarly journals Sympathetic and cardiovascular responses to venous distension in an occluded limb

2011 ◽  
Vol 301 (6) ◽  
pp. R1831-R1837 ◽  
Author(s):  
Jian Cui ◽  
Urs A. Leuenberger ◽  
Zhaohui Gao ◽  
Lawrence I. Sinoway
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Present Report ◽  
Muscle Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Saline Infusion ◽  
Nerve Activity ◽  
Sympathetic Response ◽  
Venous Circulation ◽  
Blood Pressure Responses

We recently showed that a fixed volume (i.e., 40 ml) of saline infused into the venous circulation of an arterially occluded vascular bed increases muscle sympathetic nerve activity (MSNA) and blood pressure. In the present report, we hypothesized that the volume and rate of infusion would influence the magnitude of the sympathetic response. Blood pressure, heart rate, and MSNA were assessed in 13 young healthy subjects during forearm saline infusions (arrested circulation). The effects of different volumes of saline (i.e., 2%, 3%, 4%, or 5% forearm volume at 30 ml/min) and different rates of infusion (i.e., 5% forearm volume at 10, 20, or 30 ml/min) were evaluated. MSNA and blood pressure responses were linked with the infusion volume. Infusion of 5% of forearm volume evoked greater MSNA responses than did infusion of 2% of forearm volume (Δ11.6 ± 1.9 vs. Δ3.1 ± 1.8 bursts/min and Δ332 ± 105 vs. Δ38 ± 32 units/min, all P < 0.05). Moreover, greater MSNA responses were evoked by saline infusion at 30 ml/min than 10 ml/min ( P < 0.05). Sonographic measurements confirmed that the saline infusions induced forearm venous distension. The results suggest that volume and rate of saline infusion are important factors in evoking sympathetic activation. We postulate that venous distension contributes to cardiovascular autonomic adjustment in humans.

Differential control of renal and splenic nerves without medullary topography

1991 ◽  
Vol 260 (4) ◽  
pp. H1072-H1079 ◽  
Author(s):  
D. J. Beluli ◽  
L. C. Weaver
Keyword(s):  
Spatial Organization ◽  
Excitatory Amino Acid ◽  
Sympathetic Nerves ◽  
Ventrolateral Medulla ◽  
Renal Nerve ◽  
Homocysteic Acid ◽  
Fixed Proportion ◽  
Excitatory Responses ◽  
Differential Control ◽  
Neuronal Groups

A previous study in our laboratory showed that pharmacological blockade of neurons in the rostral ventrolateral medulla has greater influence on the electrical activity of renal than splenic nerves (K. Hayes and L. C. Weaver, J. Physiol. Lond. 428: 371-385, 1990). This differential control of sympathetic nerves innervating different organs may be due to viscerotopic representation of the kidney and spleen within medullary neurons that control the vasculature. To search for this topographical organization, 15 nl (2.5 nmol) of the excitatory amino acid DL-homocysteic acid (DLH) was microinjected into the ventrolateral medulla (VLM) of rats anesthetized with urethan. No distinct viscerotopic organization was found in the rostral or caudal VLM. However, renal nerve responses were consistently greater than splenic by a fixed proportion. In summary, stimulation of rostral and caudal VLM neurons causes differential renal and splenic excitatory responses, but mechanisms providing this selective control do not involve spatial organization of neuronal groups in the VLM.

Spinal NMDA receptors mediate pressor responses evoked from the rostral ventrolateral medulla

1991 ◽  
Vol 260 (1) ◽  
pp. H267-H275 ◽  
Author(s):  
M. K. Bazil ◽  
F. J. Gordon
Keyword(s):  
Spinal Cord ◽  
Heart Rate ◽  
Nmda Receptors ◽  
Excitatory Amino Acid ◽  
Cardiovascular Responses ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Pressor Responses

These studies investigated the role of spinal N-methyl-D-aspartic acid (NMDA) receptors in the mediation of cardiovascular responses evoked by L-glutamate (L-Glu) stimulation of the rostral ventrolateral medulla (RVM). Microinjections of L-Glu into the RVM of urethan-anesthetized rats increased mean arterial pressure (MAP) and heart rate. Intrathecal administration of the NMDA receptor antagonists D-(-)-2-amino-7-phosphonoheptanoic acid (D-AP-7) or 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) reduced MAP and heart rate. Blockade of NMDA receptors by D-AP-7 or CPP in the caudal thoracic spinal cord markedly reduced RVM pressor responses with little effect on evoked tachycardia. Administration of D-AP-7 to the rostral thoracic spinal cord had no effect on RVM pressor or tachycardic responses. Intrathecal D-AP-7 and CPP abolished the cardiovascular effects of intrathecal NMDA without reducing those produced by intrathecal kainic acid or the quisqualate agonist DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). These results indicate that 1) tonic activation of spinal NMDA receptors participates in the maintenance of sympathetic outflow to the heart and blood vessels, 2) pressor responses evoked from the RVM require synaptic activation of spinal NMDA receptors, and 3) an excitatory amino acid may be the neurotransmitter of pressor pathways descending from the RVM to the spinal cord.

scholarly journals Exaggerated cardiovascular responses to muscle contraction and tendon stretch in UCD type-2 diabetes mellitus rats

2019 ◽  
Vol 317 (2) ◽  
pp. H479-H486 ◽  
Author(s):  
Ann-Katrin Grotle ◽  
Charles K. Crawford ◽  
Yu Huo ◽  
Kai M. Ybarbo ◽  
Michelle L. Harrison ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Responses ◽  
Exercise Pressor Reflex ◽  
Static Contraction ◽  
Pressor Reflex ◽  
Blood Pressure Responses

Patients with type-2 diabetes mellitus (T2DM) have exaggerated sympathetic activity and blood pressure responses to exercise. However, the underlying mechanisms for these responses, as well as how these responses change throughout disease progression, are not completely understood. For this study, we examined the effect of the progression of T2DM on the exercise pressor reflex, a critical neurocardiovascular mechanism that functions to increase sympathetic activity and blood pressure during exercise. We also aimed to examine the effect of T2DM on reflexive cardiovascular responses to static contraction, as well as those responses to tendon stretch when an exaggerated exercise pressor reflex was present. We evoked the exercise pressor reflex and mechanoreflex by statically contracting the hindlimb muscles and stretching the Achilles tendon, respectively, for 30 s. We then compared pressor and cardioaccelerator responses in unanesthetized, decerebrated University of California Davis (UCD)-T2DM rats at 21 and 31 wk following the onset of T2DM to responses in healthy nondiabetic rats. We found that the pressor response to static contraction was greater in the 31-wk T2DM [change in mean arterial pressure (∆MAP) = 39 ± 5 mmHg] but not in the 21-wk T2DM (∆MAP = 24 ± 5 mmHg) rats compared with nondiabetic rats (∆MAP = 18 ± 2 mmHg; P < 0.05). Similarly, the pressor and the cardioaccelerator responses to tendon stretch were significantly greater in the 31-wk T2DM rats [∆MAP = 69 ± 6 mmHg; change in heart rate (∆HR) = 28 ± 4 beats/min] compared with nondiabetic rats (∆MAP = 14 ± 2 mmHg; ∆HR = 5 ± 3 beats/min; P < 0.05). These findings suggest that the exercise pressor reflex changes as T2DM progresses and that a sensitized mechanoreflex may play a role in exaggerating these cardiovascular responses. NEW & NOTEWORTHY This is the first study to provide evidence that as type-2 diabetes mellitus (T2DM) progresses, the exercise pressor reflex becomes exaggerated, an effect that may be due to a sensitized mechanoreflex. Moreover, these findings provide compelling evidence suggesting that impairments in the reflexive control of circulation contribute to exaggerated blood pressure responses to exercise in T2DM.

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