Nociceptin in rVLM mediates electroacupuncture inhibition of cardiovascular reflex excitatory response in rats

2005 ◽  
Vol 98 (6) ◽  
pp. 2056-2063 ◽  
Author(s):  
Melissa M. Crisostomo ◽  
Peng Li ◽  
Stephanie C. Tjen-A-Looi ◽  
John C. Longhurst
Keyword(s):  
Blood Pressure ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Pressor Response ◽  
Inhibitory Effect ◽  
Reflex Response ◽  
Ventrolateral Medulla ◽  
Gastric Distension ◽  
Sprague Dawley ◽  
Nociceptin Receptor

Electroacupuncture (EA) at Neiguan-Jianshi acupoints through an opioid mechanism inhibits the cardiovascular pressor response induced by mechanical stimulation of the stomach. Because nociceptin also may regulate cardiovascular activity through its action in the brain stem, we hypothesized that this neuromodulator serves a role in the EA-related inhibitory effect. Blood pressure in ventilated male Sprague-Dawley rats (400–600 g) anesthetized by ketamine and α-chloralose was measured during balloon inflation of the stomach. Gastric distension with 6–8 ml of air induced consistent pressor reflexes of 26 ± 1 mmHg that could be repeated every 10 min for 100 min. When nociceptin (10 nM) was microinjected into the rostral ventrolateral medulla (rVLM), the pressor response induced by gastric distension was inhibited by 68 ± 6%. Thirty minutes of EA also decreased the reflex response by 75 ± 11%; microinjection of saline into the rVLM did not alter the inhibitory effect of EA. In contrast, microinjection of a nociceptin receptor antagonist into the rVLM promptly reversed the EA response. Pretreatment with the opioid receptor antagonist naloxone did not influence the EA-like inhibitory effect of nociceptin on the distension-induced pressor reflex (22 ± 1 to 8 ± 2 mmHg). Furthermore, a μ-opioid receptor agonist microinjected into the rVLM after microinjection of a nociceptin receptor antagonist during EA promptly reversed the nociceptin receptor antagonist-related inhibition of the EA effect. Thus, in addition to the classical opioid system, nociceptin, through opioid receptor-like-1 receptor stimulation in the rVLM, participates in the modulatory influence of EA on reflex-induced increases in blood pressure.

Naloxone reverses inhibitory effect of electroacupuncture on sympathetic cardiovascular reflex responses

1999 ◽  
Vol 276 (6) ◽  
pp. H2127-H2134 ◽  
Author(s):  
Dong M. Chao ◽  
Lin L. Shen ◽  
Stephanie Tjen-A-Looi ◽  
Koullis F. Pitsillides ◽  
Peng Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Inhibitory Effect ◽  
Reflex Response ◽  
Ventrolateral Medulla ◽  
Arterial Blood ◽  
Cardiovascular Reflex ◽  
Wide Range ◽  
Feline Model ◽  
Stimulation Of

Acupuncture and electroacupuncture (EA) have been used in traditional Chinese medicine to treat a wide range of diseases and conditions, including angina pectoris and myocardial infarction. In a feline model of reflex-induced reversible myocardial ischemia, electrical stimulation of the median nerves to mimic EA (Neiguan acupoint) significantly improved ischemic dysfunction, secondary to an inhibitory effect of EA on reflex pressor effects evoked by bradykinin (BK). The central mechanism of EA’s inhibitory effect in this model is unknown. Accordingly, in α-chloralose-anesthetized cats, BK (10 μg/ml) was applied to the gallbladder to elicit a cardiovascular reflex response that significantly ( P < 0.05) increased arterial blood pressure and heart rate; normalized systolic wall thickening (%WTh) of the left ventricle, measured by ultrasonic single-crystal sonomicrometer, increased by 31 ± 11% ( P < 0.05). After ligation of a side branch of the left anterior descending coronary artery, the reflex pressor response to BK resulted in a significant decrease of %WTh (−32 ± 6%) in the ischemic region. When bilateral EA of the Neiguan acupoints was performed, the pressor response to BK was inhibited and regional myocardial function was significantly improved (+19 ± 20%). The inhibitory effects of EA on blood pressure and %WTh were reversed by intravenous injection of naloxone (0.4 mg/kg; n = 9) or microinjection of naloxone (10 nM in 0.1 μl/site; n= 14) into the rostral ventrolateral medulla (rVLM). Thus %WTh with intravenous naloxone was reduced to −13 ± 29% ( P<0.05) during stimulation of the gallbladder. Our results indicate that the inhibitory effect of EA on the BK-induced pressor response and the consequent improvement of ischemic dysfunction is dependent on the activation of opioid receptors, specifically receptors located in the rVLM.

Effect of electroacupuncture on pressor reflex during gastric distension

2002 ◽  
Vol 283 (6) ◽  
pp. R1335-R1345 ◽  
Author(s):  
Peng Li ◽  
Kasra Rowshan ◽  
Melissa Crisostomo ◽  
Stephanie C. Tjen-A-Looi ◽  
John C. Longhurst
Keyword(s):  
Peroneal Nerve ◽  
Cardiovascular Response ◽  
Pressor Response ◽  
Gastric Wall ◽  
Ventrolateral Medulla ◽  
Gastric Distension ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stomach Meridian ◽  
Pressor Reflex

The effect of electroacupuncture (EA) on the reflex cardiovascular response induced by mechanical distension of the stomach was studied in ventilated male Sprague-Dawley rats anesthetized by ketamine and α-chloralose. Repeated balloon inflation of the stomach to produce 20 mmHg tension on the gastric wall induced a consistent rise in mean arterial pressure, while heart rate (372 ± 22 beats/min) was unchanged. This response was reversed by transection of the splanchnic nerves. Bilateral application of EA (1–2 mA, 2 Hz) at Neiguan-Jianshi acupoints (pericardial meridian, Pe 5–6) over the median nerve for 30 min significantly decreased the pressor response from 33 ± 6 to 18 ± 4 mmHg ( n = 7, P < 0.05). This effect began after 10 min of EA and continued for 40 min after termination of EA. EA at Zusanli-Shangquxu acupoints (stomach meridian, St 36–37) over the deep peroneal nerve similarly inhibited the pressor response. The effect lasted for 10 min after EA was stopped ( n = 6, P < 0.05), while EA at Guangming-Xuanzhong acupoints (gallbladder meridian, GB 37–39) over the superficial peroneal nerve did not inhibit the pressor response. Naloxone injected intravenously ( n = 6) immediately after termination of EA or administered by microinjection into the rostral ventrolateral medulla (rVLM) 25 min after initiation of EA ( n = 6) reversed the inhibition by EA, suggesting an opiate mechanism, including the rVLM, was involved.

scholarly journals Spinal nociceptin mediates electroacupuncture-related modulation of visceral sympathoexcitatory reflex responses in rats

2009 ◽  
Vol 297 (2) ◽  
pp. H859-H865 ◽  
Author(s):  
Wei Zhou ◽  
Aman Mahajan ◽  
John C. Longhurst
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Intrathecal Injection ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Gastric Distension ◽  
Reflex Modulation ◽  
Reflex Responses ◽  
Pressor Responses ◽  
Pressor Reflex

The role of nociceptin and its spinal cord neural pathways in electroacupuncture (EA)-related inhibition of visceral excitatory reflexes is not clear. Nociceptin/orphanin FQ (N/OFQ) is an endogenous ligand for a G protein-coupled receptor, called the N/OFQ peptide (NOP) receptor, which has been found to be distributed in the spinal cord. The present study investigated the importance of this system in visceral-cardiovascular reflex modulation during EA. Cardiovascular pressor reflex responses were induced by gastric distension in Sprague-Dawley rats anesthetized by ketamine and xylazine. An intrathecal injection of nociceptin (10 nM) at T1–2 attenuated the pressor responses by 35%, similar to the influence of EA at P 5–6 (42% decrease). An intrathecal injection of the NOP antagonist, [ N-Phe1]nociceptin1-13 NH2, partially reversed the EA response. Pretreatment with the opioid receptor antagonist naloxone did not alter the EA-like inhibitory effect of nociceptin on the pressor reflex, whereas a combination of nociceptin receptor antagonist with naloxone completely abolished the EA response. An intrathecal injection of nociceptin attenuated the pressor responses to the electrical stimulation of the rostral ventrolateral medulla by 46%, suggesting that nociceptin can regulate sympathetic outflow. Furthermore, a bilateral microinjection of NOP antagonist into either the dorsal horn or the intermediolateral column at T1 partially reversed the EA inhibitory effect. These results suggest that nociceptin in the spinal cord mediates part of the EA-related modulation of visceral reflex responses.

The sympathoinhibitory effects of systemic cholecystokinin are dependent on neurons in the caudal ventrolateral medulla in the rat

2006 ◽  
Vol 291 (5) ◽  
pp. R1390-R1398 ◽  
Author(s):  
D. M. Sartor ◽  
A. J. M. Verberne
Keyword(s):  
Sympathetic Nerve ◽  
Excitatory Amino Acid ◽  
Inhibitory Effect ◽  
Reflex Response ◽  
Ventrolateral Medulla ◽  
Gastrointestinal Hormone ◽  
Sprague Dawley ◽  
Neuronal Inhibition ◽  
Before And After ◽  
Nerve Discharge

The gastrointestinal hormone CCK inhibits a subset of presympathetic neurons in the rostroventrolateral medulla (RVLM) that may be responsible for driving the sympathetic vasomotor outflow to the gastrointestinal circulation. We tested the hypothesis that the central neurocircuitry of this novel sympathoinhibitory reflex involves a relay in the caudal ventrolateral medullary (CVLM) depressor area. Blood pressure and greater splanchnic sympathetic nerve discharge (SSND) or lumbar sympathetic nerve discharge (LSND) were monitored in anesthetised, paralyzed male Sprague-Dawley rats. The effects of phenylephrine (PE, 10 μg/kg iv; baroreflex activation), phenylbiguanide (PBG, 10 μg/kg iv; von Bezold-Jarisch reflex) and CCK (4 or 8 μg/kg iv) on SSND or LSND, were tested before and after bilateral injection of 50–100 nl of the GABAA agonist muscimol (1.75 mM; n = 6, SSND; n = 7, LSND) or the excitatory amino acid antagonist kynurenate (55 mM; n = 7, SSND) into the CVLM. PE and PBG elicited splanchnic and lumbar sympathoinhibitory responses that were abolished by bilateral muscimol or kynurenate injection into the CVLM. Similarly, the inhibitory effect of CCK on SSND was abolished after neuronal inhibition within the CVLM. In contrast, CCK-evoked lumbar sympathoexcitation was accentuated following bilateral CVLM inhibition. In control experiments ( n = 7), these agents were injected outside the CVLM and had no effect on splanchnic sympathoinhibitory responses to PE, PBG, and CCK. In conclusion, neurons in the CVLM are necessary for the splanchnic but not lumbar sympathetic vasomotor reflex response to CCK. This strengthens the view that subpopulations of RVLM neurons supply sympathetic vasomotor outflow to specific vascular territories.

Neurotransmission in the medulla mediating insular cortical and lateral hypothalamic sympathetic responses

1998 ◽  
Vol 76 (7-8) ◽  
pp. 737-746 ◽  
Author(s):  
Kenneth S Butcher ◽  
David F Cechetto
Keyword(s):  
Receptor Antagonist ◽  
Sympathetic Nerve ◽  
Pressor Response ◽  
Ventrolateral Medulla ◽  
Bipolar Electrode ◽  
Hypothalamic Area ◽  
Renal Nerve ◽  
Lateral Hypothalamic ◽  
Baseline Activity ◽  
Sympathetic Responses

Previous evidence has shown sympathetic nerve responses to insular cortical (IC) stimulation are mediated by synapses within the lateral hypothalamic area (LHA) and ventrolateral medulla (VLM). The present study was aimed at determining the neurotransmitter(s) and receptor(s) involved at the synapse in the VLM. Twenty male Wistar rats were instrumented for renal nerve, arterial pressure, and heart rate recording. The IC or the LHA was stimulated with a bipolar electrode (200-1000 µA; 2 ms; 0.8 Hz) to elicit sympathetic nerve responses. Antagonists were then pressure-injected into the VLM (300 nL). Bilateral and unilateral kynurenate (25 mM) resulted in 100% block of IC- and LHA-stimulated sympathetic nerve responses. Bilateral injection of the non-NMDA (N-methyl-D-aspartate) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 200 µM) also resulted in up to 100% block of IC and LHA sympathetic responses. In addition, unilateral injections of CNQX were made in two animals, resulting in 100 and 83% block of LHA sympathetic responses. Bilateral injection of the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5; 200µM) did not affect the response to IC or LHA stimulation. Kynurenate, CNQX, and AP5 all resulted in an elevation of baseline sympathetic nerve activity and a pressor response. Kynurenate resulted in a 263 ± 79% increase in baseline activity, while CNQX and AP5 resulted in 83 ± 19% and 91 ± 21% increases, respectively. Bilateral injections of antagonists for GABAA (bicuculline; 0.1 µM), acetylcholine (atropine; 0.1 µM) and catecholaminergic alpha and beta receptors (phentolamine and propranolol: 0.1 µM) had no effect on LHA sympathetic responses. Thus, sympathetic responses originating in the IC and LHA are mediated by a non-NMDA receptors in the VLM, which are likely AMPA receptors.Key words: insular cortex, ventrolateral medulla, glutamate, sympathetic activity.

scholarly journals Rostral ventral medulla 5-HT1A receptors selectively inhibit the somatosympathetic reflex

2001 ◽  
Vol 280 (5) ◽  
pp. R1261-R1268 ◽  
Author(s):  
Takashi Miyawaki ◽  
Ann K. Goodchild ◽  
Paul M. Pilowsky
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Arterial Blood ◽  
Potent Inhibition ◽  
Somatosympathetic Reflex

The role of the 5-hydroxytryptamine (5-HT1A) receptors in the rostral ventrolateral medulla (RVLM) on somatosympathetic, baroreceptor, and chemoreceptor reflexes was examined in anesthetized rats. Microinjection of the selective 5-HT1A agonist 8-hydroxy-di- n-propylamino tetralin (8-OH-DPAT) decreased arterial blood pressure and splanchnic sympathetic nerve activity (SNA). Electrical stimulation of the hindlimb evoked early and late excitatory sympathetic responses. Bilateral microinjection in the RVLM of 8-OH-DPAT markedly attenuated both the early and late responses. This potent inhibition of the somatosympathetic reflex persisted even after SNA and arterial blood pressure returned to preinjection levels. Preinjection of the selective 5-HT1A antagonist NAN-190 in the RVLM blocked the sympathoinhibitory effect of 8-OH-DPAT and attenuated the inhibitory effect on the somatosympathetic reflex. 8-OH-DPAT injected in the RVLM did not affect baroreceptor or chemoreceptor reflexes. Our findings suggest that activation of 5-HT1A receptors in the RVLM exerts a potent, selective inhibition on the somatosympathetic reflex.

scholarly journals Overexpression of Central ACE2 (Angiotensin-Converting Enzyme 2) Attenuates the Pressor Response to Chronic Central Infusion of Ang II (Angiotensin II)

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1514-1525
Author(s):  
Anyun Ma ◽  
Lie Gao ◽  
Ahmed M. Wafi ◽  
Li Yu ◽  
Tara Rudebush ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Pressor Response ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Intracerebroventricular Infusion

We investigated the mechanism by which ACE2 (angiotensin-converting enzyme 2) overexpression alters neurohumoral outflow and central oxidative stress. Nrf2 (nuclear factor [erythroid-derived 2]-like 2) is a master antioxidant transcription factor that regulates cytoprotective and antioxidant genes. We hypothesized that upregulation of central ACE2 inhibits the pressor response to Ang II (angiotensin II) by reducing reactive oxygen species through a Nrf2/antioxidant enzyme–mediated mechanism in the rostral ventrolateral medulla. Synapsin human Angiotensin Converting Enzyme 2 positive (SynhACE2 +/+ ) mice and their littermate controls synhACE2 −/− were used to evaluate the consequence of intracerebroventricular infusion of Ang II. In control mice, Ang II infusion evoked a significant increase in blood pressure and norepinephrine excretion, along with polydipsia and polyuria. The pressor effect of central Ang II was completely blocked in synhACE2 +/+ mice. Polydipsia, norepinephrine excretion, and markers of oxidative stress in response to central Ang II were also reduced in synhACE2 +/+ mice. The MasR (Mas receptor) agonist Ang 1–7 and blocker A779 had no effects on blood pressure. synhACE2 +/+ mice showed enhanced expression of Nrf2 in the rostral ventrolateral medulla which was blunted following Ang II infusion. Ang II evoked nuclear translocation of Nrf2 in cultured Neuro 2A (N2A) cells. In synhACE2 −/− mice, the central Ang II pressor response was attenuated by simultaneous intracerebroventricular infusion of the Nrf2 activator sulforaphane; blood pressure was enhanced by knockdown of Nrf2 in the rostral ventrolateral medulla in Nrf2 floxed (Nrf2 f/f ) mice. These data suggest that the hypertensive effects of intracerebroventricular Ang II are attenuated by selective overexpression of brain synhACE2 and may be mediated by Nrf2-upregulated antioxidant enzymes in the rostral ventrolateral medulla.

Changes in angiotensin type 1 receptor binding and angiotensin-induced pressor responses in the rostral ventrolateral medulla of angiotensinogen knockout mice

2010 ◽  
Vol 298 (2) ◽  
pp. R411-R418 ◽  
Author(s):  
Daian Chen ◽  
Lisa Hazelwood ◽  
Lesley L. Walker ◽  
Brian J. Oldfield ◽  
Michael J. McKinley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Receptor Binding ◽  
Knockout Mice ◽  
Pressor Response ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Wild Type ◽  
Intravenous Injections ◽  
Angiotensin Type

ANG II, the main circulating effector hormone of the renin-angiotensin system, is produced by enzymatic cleavage of angiotensinogen. The present study aimed to examine whether targeted deletion of the angiotensinogen gene ( Agt) altered brain ANG II receptor density or responsiveness to ANG II. In vitro autoradiography was used to examine the distribution and density of angiotensin type 1 (AT1) and type 2 receptors. In most brain regions, the distribution and density of angiotensin receptors were similar in brains of Agt knockout mice ( Agt −/− ) and wild-type mice. In Agt −/− mice, a small increase in AT1 receptor binding was observed in the rostral ventrolateral medulla (RVLM), a region that plays a critical role in blood pressure regulation. To examine whether Agt −/− mice showed altered responses to ANG II, blood pressure responses to intravenous injection (0.01–0.1 μg/kg) or RVLM microinjection (50 pmol in 50 nl) of ANG II were recorded in anesthetized Agt −/− and wild-type mice. Intravenous injections of phenylephrine (4 μg/kg and 2 μg/kg) were also made in both groups. The magnitude of the pressor response to intravenous injections of ANG II or phenylephrine was not different between Agt −/− and wild-type mice. Microinjection of ANG II into the RVLM induced a pressor response, which was significantly smaller in Agt −/− compared with wild-type mice (+10 ± 1 vs. +23 ± 4 mmHg, respectively, P = 0.004). Microinjection of glutamate into the RVLM (100 pmol in 10 nl) produced a robust pressor response, which was not different between Agt −/− and wild-type mice. A diminished response to ANG II microinjection in the RVLM of Agt −/− mice, despite an increased density of AT1 receptors suggests that signal transduction pathways may be altered in RVLM neurons of Agt −/− mice, resulting in attenuated cellular excitation.

Protection of cardiac myocytes via δ1-opioid receptors, protein kinase C, and mitochondrial KATP channels

2001 ◽  
Vol 280 (1) ◽  
pp. H377-H383 ◽  
Author(s):  
Joon Huh ◽  
Garrett J. Gross ◽  
Hiroshi Nagase ◽  
Bruce T. Liang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Receptor Antagonist ◽  
Cardiac Myocytes ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Inhibitory Effect ◽  
Cardioprotective Effect ◽  
Opioid Receptor Antagonist ◽  
Kinase C

The objective of the present study was to investigate the role of δ1-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate whether protein kinase C and mitochondrial ATP-sensitive K+(KATP) channels act downstream of the δ1-opioid receptor in mediating this beneficial effect. A 5-min preexposure to the selective δ1-opioid receptor agonist (−)-TAN-67 (1 μM) resulted in less myocyte injury during the subsequent prolonged ischemia compared with untreated myocytes. 7-Benzylidenenaltrexone, a selective δ1-opioid receptor antagonist, completely blocked the cardioprotective effect of (−)-TAN-67. Naltriben methanesulfonate, a selective δ2-opioid receptor antagonist, had only a slight inhibitory effect on (−)-TAN-67-mediated cardioprotection. Nor-binaltorphimine dihydrochloride, a κ-opioid receptor antagonist, did not affect (−)-TAN-67-mediated cardioprotection. The protein kinase C inhibitor chelerythrine and the KATP channel inhibitors glibenclamide, a nonselective KATP antagonist, and 5-hydroxydecanoic acid, a mitochondrial selective KATPantagonist, reversed the cardioprotective effect of (−)-TAN-67. These results suggest that the δ1-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial KATP channel.

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