scholarly journals GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

2015 ◽  
Vol 309 (1) ◽  
pp. H174-H184 ◽  
Author(s):  
Vineet C. Chitravanshi ◽  
Kazumi Kawabe ◽  
Hreday N. Sapru

We have previously reported that stimulation of the hypothalamic arcuate nucleus (ARCN) by microinjections of N-methyl-d-aspartic acid (NMDA) elicits tachycardia, which is partially mediated via inhibition of vagal inputs to the heart. The neuronal pools and neurotransmitters in them mediating tachycardia elicited from the ARCN have not been identified. We tested the hypothesis that the tachycardia elicited from the ARCN may be mediated by inhibitory neurotransmitters in the nucleus ambiguus (nAmb). Experiments were done in urethane-anesthetized, artificially ventilated, male Wistar rats. In separate groups of rats, unilateral and bilateral microinjections of muscimol (1 mM), gabazine (0.01 mM), and strychnine (0.5 mM) into the nAmb significantly attenuated tachycardia elicited by unilateral microinjections of NMDA (10 mM) into the ARCN. Histological examination of the brains showed that the microinjections sites were within the targeted nuclei. Retrograde anatomic tracing from the nAmb revealed direct bilateral projections from the ARCN and hypothalamic paraventricular nucleus to the nAmb. The results of the present study suggest that tachycardia elicited by stimulation of the ARCN by microinjections of NMDA is mediated via GABAA and glycine receptors located in the nAmb.

2017 ◽  
Vol 68 (2) ◽  
pp. 129-136 ◽  
Author(s):  
Mariko So ◽  
Hirofumi Hashimoto ◽  
Reiko Saito ◽  
Yukiyo Yamamoto ◽  
Yasuhito Motojima ◽  
...  

Abstract Orexin-A and -B, and ghrelin are potent orexigenic peptides. The effects of ACT462206, a novel dual orexin receptor antagonist (DORA), on ghrelin-induced feeding were examined in adult male Wistar rats. Hyperphagia induced by the intracerebroventricular (icv) administration of ghrelin was significantly suppressed for at least 2 h by pretreatment with icv administration of DORA. A marked increase was observed in the number of neurons showing Fos immunoreactivity in the paraventricular nucleus, arcuate nucleus and lateral hypothalamic area (LHA), 90 min after icv administration of ghrelin. Pretreatment with DORA significantly decreased the number of Fos-immunoreactive (IR) neurons; however, Fos immunoreactivity remained significantly increased. Double-immunostaining for Fos and orexin-A showed that many orexin-A-IR neurons in the LHA coexisted with Fos immunoreactivity after icv administration of ghrelin, but their number was reduced significantly by DORA pretreatment. These results suggest that centrally administered ghrelin may activate the orexinergic and non-orexinergic pathways responsible for the regulation of feeding.


2016 ◽  
Vol 311 (2) ◽  
pp. H433-H444 ◽  
Author(s):  
Vineet C. Chitravanshi ◽  
Kazumi Kawabe ◽  
Hreday N. Sapru

Hypothalamic arcuate nucleus (ARCN) stimulation elicited increases in sympathetic nerve activity (IBATSNA) and temperature (TBAT) of interscapular brown adipose tissue (IBAT). The role of hypothalamic dorsomedial (DMN) and paraventricular (PVN) nuclei in mediating these responses was studied in urethane-anesthetized, artificially ventilated, male Wistar rats. In different groups of rats, inhibition of neurons in the DMN and PVN by microinjections of muscimol attenuated the increases in IBATSNA and TBAT elicited by microinjections of N-methyl-d-aspartic acid into the ipsilateral ARCN. In other groups of rats, blockade of ionotropic glutamate receptors by combined microinjections of D(-)-2-amino-7-phosphono-heptanoic acid (D-AP7) and NBQX into the DMN and PVN attenuated increases in IBATSNA and TBAT elicited by ARCN stimulation. Blockade of melanocortin 3/4 receptors in the DMN and PVN in other groups of rats resulted in attenuation of increases in IBATSNA and TBAT elicited by ipsilateral ARCN stimulation. Microinjections of Fluoro-Gold into the DMN resulted in retrograde labeling of cells in the ipsilateral ARCN, and some of these cells contained proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH), or vesicular glutamate transporter-3. Since similar projections from ARCN to the PVN have been reported by us and others, these results indicate that neurons containing POMC, α-MSH, and glutamate project from the ARCN to the DMN and PVN. Stimulation of ARCN results in the release of α-MSH and glutamate in the DMN and PVN which, in turn, cause increases in IBATSNA and TBAT.


2019 ◽  
Vol 53 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Nazli Khajehnasiri ◽  
Homayoun Khazali ◽  
Farzam Sheikhzadeh ◽  
Mahnaz Ghowsi

AbstractObjective. The hypothalamic arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) circuitries are involved in the inhibition and stimulation of the appetite, respectively. The aim of this study was to investigate the effects of one-month lasting high-intensity exercise on the POMC mRNA and NPY mRNA expression in the above-mentioned brain structure and appetite and food intake levels.Methods. Fourteen male Wistar rats (250±50 g) were used and kept in the well-controlled conditions (22±2 °C, 50±5% humidity, and 12 h dark/light cycle) with food and water ad libitum. The rats were divided into two groups (n=7): 1) control group (C, these rats served as controls) and 2) exercised group (RIE, these rats performed a high-intensity exercise for one month (5 days per week) 40 min daily with speed 35 m/min. The total exercise time was 60 min. The body weight and food intake were recorded continuously during the experiments.Results. The results showed relative mRNA expression of POMC and NPY estimated in the hypothalamic arcuate nucleus. There were no significant differences in the NPY and POMC mRNAs expression levels and food intake between C and RIE groups.Conclusions. The present data indicate that one-month regular intensive exercise did not alter the levels of NPY and POMC mRNAs expression (as two important factors in the regulation of appetite) in the hypothalamic arcuate nucleus and food intake suggesting that this type of exercise itself is not an appropriate procedure for the body weight reduction.


1990 ◽  
Vol 259 (3) ◽  
pp. R579-R584 ◽  
Author(s):  
S. Rivest ◽  
D. Richard

The effects of a hypothalamic paraventricular nucleus (PVN) lesion on energy balance were investigated in exercise-trained rats. Male Wistar rats weighing initially 250 g were divided into four groups. Two groups of rats underwent a bilateral PVN lesion, whereas the two remaining groups were sham operated. The PVN lesions were done electrolytically. One group from each surgical treatment was exercised, while the other group was kept in sedentary conditions. Rats were exercised on a rodent motor-driven treadmill at moderate intensity, 1 h/day for 21 consecutive days. Food intake and body weight were measured each day during the study. At the end of the treatment period, rats were killed, and carcasses were analyzed for their energy content. Serum corticosterone was measured by a competitive protein-binding assay. Energy gain and energy intake were lower in exercised rats than in sedentary controls, regardless of whether they were sham or PVN lesioned. Concurrently, there was no difference in the energy gain between PVN-lesioned and sham-operated rats, despite the fact that PVN-lesioned rats ended the experiment with a larger body weight than the sham-lesioned animals. Serum corticosterone levels were lower in PVN-lesioned rats than in sham-lesioned rats. In conclusion, the present results indicate that the PVN, the hypothalamic nucleus predominantly controlling the pituitary-adrenal axis activity, is not a prominent structure in the regulation of energy balance in exercised male Wistar rats.


2003 ◽  
Vol 284 (6) ◽  
pp. R1611-R1620 ◽  
Author(s):  
John Ciriello ◽  
Cleusa V. R. de Oliveira

Although recent studies have reported hypocretin 1 (hcrt-1)-like-immunoreactivity (ir) within the region of the nucleus ambiguus (Amb) in the caudal brain stem, the function of hcrt-1 in the Amb on cardiovascular function is not known. Three series of experiments were done in male Wistar rats to investigate the effects of microinjections of hcrt-1 into Amb on heart rate (HR), mean arterial pressure (MAP), and the arterial baroreceptor reflex. In the first series, a detailed mapping of the distribution of hcrt-1- and hcrt-1 receptor (hcrtR-1)-like-ir was obtained of the Amb region. Although hcrt-1-like- and hcrtR-1-like-ir were found throughout the rostrocaudal extent of the Amb and adjacent ventrolateral medullary reticular formation, most of the hcrtR-1-like-ir was observed in the area just ventral to the compact formation of Amb, in the region of the external formation of the nucleus (Ambe). In the second series, the Amb region that contained hcrt-1 and hcrtR-1-ir was explored for sites that elicited changes in HR and MAP in urethane and α-chloralose-anesthetized rats. Microinjections of hcrt-1 (0.5–2.5 pmol) into the Ambe elicited a dose-related decrease in HR, with little or no direct change in MAP. The small decreases in MAP were found to be secondary to the HR changes. The largest bradycardia responses were elicited from sites in the Ambe. Administration (iv) of the muscarinic receptor antagonist atropine methyl bromide or ipsilateral vagotomy abolished the HR response, indicating that the HR response was due to activation of vagal cardiomotor neurons. In the final series, microinjections of hcrt-1 into the Ambe significantly potentiated the reflex bradycardia elicited by activation of the baroreflex as a result of the increased MAP after the intravenous injection of phenylephrine. These data suggest that hcrt-1 in the Ambe activates neuronal systems that alter the excitability of central circuits that reflexly control the circulation through the activation of vagal preganglionic cardioinhibitory neurons.


2011 ◽  
Vol 300 (3) ◽  
pp. H951-H960 ◽  
Author(s):  
Hideki Arakawa ◽  
Vineet C. Chitravanshi ◽  
Hreday N. Sapru

The hypothalamic arcuate nucleus (ARCN) has been reported to play a significant role in cardiovascular regulation. It has been hypothesized that the ARCN may be one of the sites of cardiovascular actions of angiotensins (ANGs). Experiments were carried out in urethane-anesthetized, artificially ventilated, adult male Wistar rats. The ARCN was identified by microinjections of N-methyl-d-aspartic acid (NMDA; 10 mM). Microinjections (50 nl) of ANG-(1–12) (1 mM) into the ARCN elicited increases in mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA). The tachycardic responses to ANG-(1–12) were attenuated by bilateral vagotomy. The cardiovascular responses elicited by ANG-(1–12) were attenuated by microinjections of ANG II type 1 receptor (AT1R) antagonists but not ANG type 2 receptor (AT2R) antagonist. Combined inhibition of ANG-converting enzyme (ACE) and chymase in the ARCN abolished ANG-(1–12)-induced responses. Microinjections of ANG II (1 mM) into the ARCN also increased MAP and HR. Inhibition of ARCN by microinjections of muscimol (1 mM) attenuated the pressor and tachycardic responses to intravenously administered ANG-(1–12) and ANG II (300 pmol/kg each). These results indicated that 1) microinjections of ANG-(1–12) into the ARCN elicited increases in MAP, HR, and GSNA; 2) HR responses were mediated via both sympathetic and vagus nerves; 3) AT1Rs, but not AT2Rs, in the ARCN mediated ANG-(1–12)-induced responses; 4) both ACE and chymase were needed to convert ANG-(1–12) to ANG II in the ARCN; and 5) ARCN plays a role in mediating the cardiovascular responses to circulating ANGs.


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