scholarly journals Activation of µ-opioid receptors in the rostral ventrolateral medulla blocks the sympathetic counterregulatory response to glucoprivation

2018 ◽  
Vol 315 (6) ◽  
pp. R1115-R1122 ◽  
Author(s):  
Zohra M. Kakall ◽  
Polina E. Nedoboy ◽  
Melissa M. J. Farnham ◽  
Paul M. Pilowsky
Keyword(s):  
Opioid Receptors ◽  
Glucose Production ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Efferent Nerve ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Adrenaline Release

Activation of neurons in the rostral ventrolateral medulla (RVLM) following glucoprivation initiates sympathoadrenal activation, adrenaline release, and increased glucose production. Here, we aimed to determine the role of RVLM µ-opioid receptors in the counterregulatory response to systemic glucoprivation. Experiments were performed in pentobarbital sodium anesthetized male Sprague-Dawley rats ( n = 30). Bilateral activation of RVLM µ-opioid receptors with [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) (8 mM, 50 nl) depressed adrenal sympathetic nerve activity for ~60 min ( n = 6; Δ49.9 ± 5.8%, P < 0.05). The counterregulatory response to glucoprivation (measured by adrenal sympathetic efferent nerve activity) induced by 2-deoxyglucose (2-DG) ( n = 6; Δ63.6 ± 16.5%, P < 0.05) was completely blocked 60 min after DAMGO microinjections ( n = 6; Δ10.2 ± 3.5%, P < 0.05). Furthermore, DAMGO pretreatment attenuated the increase in blood glucose levels after 2-DG infusion ( n = 6; 6.1 ± 0.7mmol/l vs. baseline 5.2 ± 0.3mmol/l, P > 0.05) compared with 2-DG alone ( n = 6; 7.6 ± 0.4mmol/l vs. baseline 6.0 ± 0.4mmol/l, P < 0.05). Thus, activation of RVLM µ-opioid receptors attenuated the neural efferent response to glucoprivation and reduced glucose production.

NK1 receptor activation in rat rostral ventrolateral medulla selectively attenuates somato-sympathetic reflex while antagonism attenuates sympathetic chemoreflex

2005 ◽  
Vol 288 (6) ◽  
pp. R1707-R1715 ◽  
Author(s):  
John M. Makeham ◽  
Ann K. Goodchild ◽  
Paul M. Pilowsky
Keyword(s):  
Substance P ◽  
Phrenic Nerve ◽  
Receptor Activation ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Nk1 Receptor ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Phrenic Nerve Activity ◽  
Arterial Blood

The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5–11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O2)11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O2)11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM.

Central KATP channels modulate glucose effectiveness in humans and rodents

2020 ◽  
Author(s):  
Ada Admin ◽  
Michelle Carey ◽  
Eric Lontchi-Yimagou ◽  
William Mitchell ◽  
Sarah Reda ◽  
...  
Keyword(s):  
Katp Channel ◽  
Glucose Production ◽  
Katp Channels ◽  
Endogenous Glucose Production ◽  
Elevated Plasma ◽  
Sprague Dawley ◽  
Glucose Effectiveness ◽  
Sprague Dawley Rats ◽  
The Central Nervous System

Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this ‘glucose effectiveness’ is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). ATP-sensitive potassium channels (K<sub>ATP</sub> channels) in the central nervous system (CNS) have been shown to regulate EGP in humans and rodents. We examined the contribution of central K<sub>ATP</sub> channels to glucose effectiveness. Under fixed hormonal conditions (‘pancreatic clamp’ studies), hyperglycemia suppressed EGP by ~50% in both non-diabetic humans and normal Sprague Dawley rats. By contrast, antagonism of K<sub>ATP</sub> channels with glyburide significantly reduced the EGP-lowering effect of hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on EGP and gluconeogenic enzymes in rats were abolished by intracerebroventricular (ICV) administration of the KATP channel agonist diazoxide. These findings indicate that about half of EGP suppression by hyperglycemia is mediated by central K<sub>ATP</sub> channels. These central mechanisms may offer a novel therapeutic target for improving glycemic control in T2D.

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.

Contribution of α2-adrenoceptors in caudal ventrolateral medulla to cardiovascular regulation in rat

1998 ◽  
Vol 274 (4) ◽  
pp. R1119-R1124 ◽  
Author(s):  
Shogo Sesoko ◽  
Hiromi Muratani ◽  
Masanobu Yamazato ◽  
Hiroshi Teruya ◽  
Shuichi Takishita ◽  
...  
Keyword(s):  
Cardiovascular Effect ◽  
Ventrolateral Medulla ◽  
Sprague Dawley ◽  
Renal Sympathetic Nerve Activity ◽  
Caudal Ventrolateral Medulla ◽  
Adrenoceptor Antagonist ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid ◽  
Cardiovascular Neurons ◽  
Selective Blocker

The inhibitory action of α2-agonists on the cardiovascular neurons has been elucidated in the rostral ventrolateral medulla (RVLM) but not in the caudal ventrolateral medulla (CVLM). Our study aimed to clarify whether microinjection of clonidine into the CVLM elicits any cardiovascular effect and whether endogenous α2-adrenoceptor-mediated mechanisms contribute to the tonic activity of the CVLM neurons. In male Sprague-Dawley rats (7–9 wk old, 270–320 g) anesthetized with urethan, unilateral microinjection of 8 nmol of clonidine into the CVLM ( n = 10) increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) by 12.1 ± 1.8 mmHg (mean ± SE, P < 0.01) and 25.8 ± 4.8% ( P < 0.01), while heart rate (HR) remained unaltered. Unilateral microinjection of 2 nmol of SKF-86466, a selective blocker of the α2-adrenoceptors, into the CVLM ( n = 10) decreased MAP, HR, and RSNA (−11.6 ± 2.6 mmHg, −26 ± 7 beats/min, and −15.3 ± 1.7%, respectively, P < 0.01 for each). Artificial cerebrospinal fluid caused neither a cardiovascular effect nor a sympathetic response. Prior injection of SKF-86466 into the ipsilateral CVLM attenuated the effects of clonidine. Bilateral microinjection of muscimol into the RVLM abolished the effects of both clonidine and SKF-86466 injected into the CVLM. The pressor and sympathoexcitatory effects of clonidine injected into the CVLM suggest a neuroinhibitory action of the drug on the CVLM neurons. In addition,the depressor and sympathoinhibitory effects of SKF-86466 injected into the CVLM indicated that activation of α2-adrenoceptors by endogenous ligand inhibits CVLM neurons. The effects of clonidine and the α2-adrenoceptor antagonist in the CVLM require the integrity of the RVLM.

scholarly journals Hypertension in Patients with Neurovascular Compression Is Associated with Increased Central Sympathetic Outflow

2002 ◽  
Vol 13 (1) ◽  
pp. 35-41
Author(s):  
Hans P. Schobel ◽  
Helga Frank ◽  
Ramin Naraghi ◽  
Helmut Geiger ◽  
Elmar Titz ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cold Pressor Test ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Neurovascular Compression ◽  
Sympathetic Outflow ◽  
Nerve Activity ◽  
Central Sympathetic Outflow

ABSTRACT. Recent data suggest a causal relationship between essential hypertension and neurovascular compression (NVC) at the rostral ventrolateral medulla. An increase of central sympathetic outflow might be an underlying pathomechanism. The sympathetic nerve activity to muscle was recorded in 21 patients with hypertension with NVC (NVC+ group) and in 12 patients with hypertension without NVC (NVC− group). Heart rate variability, respiratory activity, BP, and central venous pressure at rest and during unloading of cardiopulmonary baroreceptors with lower-body negative pressure and during a cold pressor test were also measured. Resting sympathetic nerve activity to muscle was twice as high in the NVC+ group compared with the NVC− group (34 ± 22 versus 18 ± 6 bursts/min; P < 0.05). Resting heart rate (P = 0.06) and low- to high-frequency power ratio values (P = NS) (as indicators of cardiac sympathovagal balance) tended to be augmented as well in the NVC+ group. The sympathetic nerve activity to muscle response to the cold pressor test was increased in the NVC+ group versus the NVC− group (+15 ± 11 versus 6 ± 12 bursts/min; P = 0.05), but hemodynamic and sympathetic nerve responses to lower-body negative pressure did not differ between the two groups. It is concluded that NVC of the rostral ventrolateral medulla in patients with essential hypertension is accompanied by increased central sympathetic outflow. Therefore, these data support the hypothesis described in the literature: in a subgroup of patients, essential hypertension might be causally related to NVC of the rostral ventrolateral medulla, at least in part, via an increase in central sympathetic outflow.

scholarly journals Arcuate nucleus injection of an anti-insulin affibody prevents the sympathetic response to insulin

2013 ◽  
Vol 304 (11) ◽  
pp. H1538-H1546 ◽  
Author(s):  
Brittany S. Luckett ◽  
Jennifer L. Frielle ◽  
Lawrence Wolfgang ◽  
Sean D. Stocker
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Arcuate Nucleus ◽  
Insulin Receptors ◽  
Ventromedial Hypothalamus ◽  
Intracerebroventricular Injection ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Sympathetic Response ◽  
Sprague Dawley Rats

Accumulating evidence suggests that insulin acts within the hypothalamus to alter sympathetic nerve activity (SNA) and baroreflex function. Although insulin receptors are widely expressed across the hypothalamus, recent evidence suggests that neurons of the arcuate nucleus (ARC) play an important role in the sympathoexcitatory response to insulin. The purpose of the present study was to determine whether circulating insulin acts directly in the ARC to elevate SNA. In anesthetized male Sprague-Dawley rats (275–425 g), the action of insulin was neutralized by microinjection of an anti-insulin affibody (1 ng/40 nl). To verify the efficacy of the affibody, ARC pretreatment with injection of the anti-insulin affibody completely prevented the increase in lumbar SNA produced by ARC injection of insulin. Next, ARC pretreatment with the anti-insulin affibody attenuated the lumbar sympathoexcitatory response to intracerebroventricular injection of insulin. Third, a hyperinsulinemic-euglycemic clamp increased lumbar, but not renal, SNA in animals that received ARC injection of a control affibody. However, this sympathoexcitatory response was absent in animals pretreated with the anti-insulin affibody in the ARC. Injection of the anti-insulin affibody in the adjacent ventromedial hypothalamus did not alter the sympathoexcitatory response to insulin. The ability of the anti-insulin affibody to prevent the sympathetic effects of insulin cannot be attributed to a general inactivation or nonspecific effect on ARC neurons as the affibody did not alter the sympathoexcitatory response to ARC disinhibition by gabazine. Collectively, these findings suggest that circulating insulin acts within the ARC to increase SNA.

134 The Effect of Adipose Derived Stromal Vascular Fraction on Stasis Zone in an Experimental Burn Model on Streptozocin – Induced Diabetic Rats

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S89-S90
Author(s):  
Cagri A Uysal ◽  
Burak Ozkan ◽  
Abbas Najimaldin Muhsun Al Bayati ◽  
Gonca Ozgun ◽  
Kadri Akinci ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Cell Density ◽  
Inflammatory Cell ◽  
Burn Injury ◽  
Stromal Vascular Fraction ◽  
Vascular Density ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats

Abstract Introduction Stasis zone is the encircling area of the coagulation zone which is a critical area determining the depth and width of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). Methods Intraperitoneal Streptozotocin was administered for the induction of diabetes mellitus (DM) and the development of DM was confirmed by the measurement of blood glucose levels in the blood samples with blood glucometer weekly 48 hours after injection. Rats with blood glucose levels above 200 mg/dl were accepted as diabetic. The diabetic animals were followed for 4 weeks before the intervention. Thermal injury was applied on dorsum of diabetic Sprague – Dawley rats (n=20) according to the previously described ‘‘comb burn’’ model. After the burn injury (30 minutes) on Sprague - Dawley rats; rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of diabetic Sprague - Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density and gradient of fibrosis were determined via immunohistochemical assay. Results Macroscopic stasis zone tissue survivability percentage (32 ± 3.28 %, 57 ± 4.28 %), average number of vessels (10.28 ± 1.28, 19.43 ± 1.72), capillary count (15.67 ± 1.97, 25.35 ± 2.15) and vascular density (1.55 ± 0.38, 2.14 ± 0.45) were higher on ADSVF side. Fibrosis gradient (1.87 ± 0.51, 1.50 ± 0.43) and inflammatory cell density (1.33 ± 0.40, 1.20 ± 0.32) were higher on the PBS side. Conclusions Macroscopic and microscopic findings determined that ADSVF has a statistically significant benefit for salvaging stasis zone on acute burn injuries in DM.

Regional effect of naltrexone in the nucleus of the solitary tract in blockade of NPY-induced feeding

2000 ◽  
Vol 278 (2) ◽  
pp. R499-R503 ◽  
Author(s):  
C. M. Kotz ◽  
M. J. Glass ◽  
A. S. Levine ◽  
C. J. Billington
Keyword(s):  
Cerebrospinal Fluid ◽  
Food Intake ◽  
Paraventricular Nucleus ◽  
Opioid Receptors ◽  
The Other ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Regional Effect ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid

Naltrexone (NLTX) in the nucleus of the solitary tract (NTS) decreases feeding induced by neuropeptide Y (NPY) in the paraventricular nucleus (PVN). We sought to determine the NTS region most sensitive to NLTX blockade of PVN NPY-induced feeding. Male Sprague-Dawley rats were fitted with two cannulas; one in the PVN and one in a hindbrain region: caudal, medial, or rostral NTS or 1 mm outside the NTS. Animals received NLTX (0, 1, 3, 10, and 30 μg in 0.3 μl) into the hindbrain region just prior to PVN NPY (0.5 μg, 0.3 μl) or artificial cerebrospinal fluid (0.3 μl). Food intake was measured at 2 h following injection. PVN NPY stimulated feeding, and NLTX in the medial NTS significantly decreased NPY-induced feeding at 2 h, whereas administration of NLTX in the other hindbrain regions did not significantly influence PVN NPY induced feeding. These data suggest that opioid receptors in the medial NTS are most responsive to feeding signals originating in the PVN after NPY stimulation.

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