scholarly journals The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

2011 ◽  
Vol 300 (3) ◽  
pp. H951-H960 ◽  
Author(s):  
Hideki Arakawa ◽  
Vineet C. Chitravanshi ◽  
Hreday N. Sapru
Keyword(s):  
Arcuate Nucleus ◽  
Cardiovascular Responses ◽  
Splanchnic Nerve ◽  
Induced Responses ◽  
Ang Ii ◽  
Vagus Nerves ◽  
Hypothalamic Arcuate Nucleus ◽  
Male Wistar Rats ◽  
Bilateral Vagotomy ◽  
Greater Splanchnic Nerve

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.

scholarly journals Cardiovascular responses elicited by a new endogenous angiotensin in the nucleus tractus solitarius of the rat

2011 ◽  
Vol 300 (1) ◽  
pp. H230-H240 ◽  
Author(s):  
Vineet C. Chitravanshi ◽  
Hreday N. Sapru
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Splanchnic Nerve ◽  
Vagus Nerves ◽  
Medial Nucleus ◽  
Male Wistar Rats ◽  
Bilateral Vagotomy ◽  
Prior Application ◽  
Greater Splanchnic Nerve

Cardiovascular effects of angiotensin-(1–12) [ANG-(1–12)] were studied in the medial nucleus of the tractus solitarius (mNTS) in anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of ANG-(1–12) (0.06 mM) into the mNTS elicited maximum decreases in mean arterial pressure (MAP; 34 ± 5.8 mmHg) and heart rate (HR; 39 ± 3.7 beats/min). Bilateral vagotomy abolished ANG-(1–12)-induced bradycardia. Efferent greater splanchnic nerve activity was decreased by microinjections of ANG-(1–12) into the mNTS. Blockade of ANG type 1 receptors (AT1Rs; using ZD-7155 or L-158,809), but not ANG type 2 receptors (AT2Rs; using PD-123319), significantly attenuated ANG-(1–12)-induced cardiovascular responses. Simultaneous inhibition of both angiotensin-converting enzyme (ACE; using captopril) and chymase (using chymostatin) completely blocked the effects of ANG-(1–12). Microinjections of A-779 [ANG-(1–7) antagonist] did not attenuate ANG-(1–12)-induced responses. Pressure ejection of ANG-(1–12) (0.06 mM, 2 nl) caused excitation of barosensitive mNTS neurons, which was blocked by prior application of the AT1R antagonist. ANG-(1–12)-induced excitation of mNTS neurons was also blocked by prior sequential applications of captopril and chymostatin. These results indicate that 1) microinjections of ANG-(1–12) into the mNTS elicited depressor and bradycardic responses by exciting barosensitive mNTS neurons; 2) the decreases in MAP and HR were mediated via sympathetic and vagus nerves, respectively; 3) AT1Rs, but not AT2Rs, mediated these actions of ANG-(1–12); 4) the responses were mediated via the conversion of ANG-(1–12) to ANG II and both ACE and chymase were involved in this conversion; and 5) ANG-(1–7) was not one of the metabolites of ANG-(1–12) in the mNTS.

scholarly journals Cardiovascular effect of angiotensin-(1–12) in the caudal ventrolateral medullary depressor area of the rat

2014 ◽  
Vol 306 (3) ◽  
pp. H438-H449 ◽  
Author(s):  
Tetsuya Kawabe ◽  
Kazumi Kawabe ◽  
Hreday N. Sapru
Keyword(s):  
Gaba Receptors ◽  
Sympathetic Nerve Activity ◽  
Cardiovascular Responses ◽  
Splanchnic Nerve ◽  
Ang Ii ◽  
Nerve Activity ◽  
Intravenous Injections ◽  
Male Wistar Rats ◽  
Greater Splanchnic Nerve

Angiotensin (ANG)-(1–12) excites neurons via ANG II type 1 receptors (AT1Rs), which are present in the caudal ventrolateral medullary depressor area (CVLM). We hypothesized that microinjections of ANG-(1–12) into the CVLM may elicit decreases in mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity. This hypothesis was tested in urethane-anesthetized adult male Wistar rats. Microinjections of ANG-(1–12) into the CVLM elicited decreases in MAP, HR, and greater splanchnic nerve activity (GSNA). ANG-(1–12)-induced responses consisted of initial (first 1–8 min) and delayed (8–24 min) phases. Prior microinjections of losartan, A-779, and captopril into the CVLM blocked initial, delayed, and both phases of ANG-(1–12) responses, respectively. Blockade of GABA receptors in the rostral ventrolateral medullary pressor area (RVLM) attenuated cardiovascular responses elicited by microinjections of ANG-(1–12) into the ipsilateral CVLM. Microinjections of ANG-(1–12) into the CVLM potentiated the reflex decreases and attenuated the reflex increases in GSNA elicited by intravenous injections of phenylephrine and sodium nitroprusside, respectively. These results indicate that microinjections of ANG-(1–12) into the CVLM elicit decreases in MAP, HR, and GSNA. Initial and delayed phases of these responses are mediated via ANG II and ANG-(1–7), respectively; the effects of ANG II and ANG-(1–7) are mediated via AT1Rs and Mas receptors, respectively. Captopril blocked both phases of ANG-(1–12) responses, indicating that angiotensin-converting enzyme is important in mediating these responses. GABA receptors in the RVLM partly mediate the cardiovascular responses to microinjections of ANG-(1–12) into the CVLM. Microinjections of ANG-(1–12) into the CVLM modulate baroreflex responses.

scholarly journals Cardiovascular responses to microinjections of urocortin 3 into the nucleus tractus solitarius of the rat

2009 ◽  
Vol 296 (2) ◽  
pp. H325-H332 ◽  
Author(s):  
Takeshi Nakamura ◽  
Kazumi Kawabe ◽  
Hreday N. Sapru
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Cardiovascular Responses ◽  
Splanchnic Nerve ◽  
Artificial Cerebrospinal Fluid ◽  
Peptide Family ◽  
Male Wistar Rats ◽  
Bilateral Vagotomy ◽  
Urocortin 3 ◽  
Greater Splanchnic Nerve

Urocortin 3 (Ucn3) is a new member of the corticotropin-releasing factor (CRF) peptide family and is considered to be a specific and endogenous ligand for CRF type 2 receptors (CRF2Rs). The presence of CRF2Rs has been reported in the nucleus tractus solitarius (NTS) of the rat. It was hypothesized that the activation of CRF2Rs in the medial NTS (mNTS) may play a role in cardiovascular regulation. This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of Ucn3 (0.03, 0.06, 0.12, and 0.25 mM) into the mNTS of anesthetized rats elicited decreases in mean arterial pressure (MAP: 5.0 ± 1.0, 21.6 ± 2.6, 20.0 ± 2.8, and 12.7 ± 3.4 mmHg, respectively) and heart rate (HR: 7.8 ± 2.6, 46.2 ± 9.3, 34.5 ± 8.4, and 16.6 ± 4.9 beats/min, respectively). Microinjections of artificial cerebrospinal fluid (100 nl) into the mNTS did not elicit cardiovascular responses. Maximum decreases in MAP and HR were elicited by 0.06 mM concentration of Ucn3. Cardiovascular responses to Ucn3 were similar in unanesthetized midcollicular decerebrate rats. A bilateral vagotomy completely abolished Ucn3-induced bradycardia. The decreases in MAP and HR elicited by Ucn3 (0.06 mM) were completely blocked by astressin (1 mM; nonselective CRFR antagonist) and K41498 (5 mM; selective CRF2R antagonist). Microinjections of Ucn3 (0.06 mM) into the mNTS decreased the efferent greater splanchnic nerve activity. After the blockade of CRF2Rs in the mNTS, a Ucn3-induced decrease in the efferent sympathetic nerve discharge was abolished. These results indicate that Ucn3 microinjections into the mNTS exerted excitatory effects on the mNTS neurons via CRF2Rs, leading to depressor and bradycardic responses.

Responses of ferret lower esophageal sphincter to 5-hydroxytryptamine: pathways and receptor subtypes

1995 ◽  
Vol 268 (6) ◽  
pp. G1004-G1011 ◽  
Author(s):  
L. A. Blackshaw ◽  
V. Nisyrios ◽  
J. Dent
Keyword(s):  
Lower Esophageal Sphincter ◽  
Splanchnic Nerve ◽  
Lower Esophageal Sphincter Pressure ◽  
Receptor Subtypes ◽  
Sphincter Pressure ◽  
In Series ◽  
Bilateral Vagotomy ◽  
Excitatory Component ◽  
Esophageal Sphincter ◽  
Greater Splanchnic Nerve

In urethananesthetized ferrets, basal lower esophageal sphincter pressure (LESP) was unaffected by the 5-hydroxytryptamine3 (5-HT3) receptor antagonist granisetron (0.5 mg/kg) or by greater splanchnic nerve section (GSX), but increased after bilateral vagotomy. Peripheral vagal nerve stimulation caused LES relaxation, often followed by a brief contraction and a prolonged inhibition of LESP. Close intra-arterial injection of 5-HT (5-100 micrograms) had a biphasic effect on LESP, with a brief drop followed by a prolonged increase. Granisetron (0.5 mg/kg i.v.) abolished the initial relaxation and revealed an earlier peak of excitation. This was not influenced by subsequent vagotomy and GSX. In a series of eight additional experiments (series 2), granisetron was given after vagotomy and GSX. In series 2, 5-HT-induced relaxation was unaffected by vagotomy but was significantly reduced after GSX and was further reduced after granisetron, indicating that 5-HT3 receptor mechanisms may lie on a sympathetic neural pathway. Vagotomy had no effect on the excitatory component. GSX had no effect on the amplitude of excitation, but reduced its latency. Granisetron had no further effect on excitation in series 2. In a separate series of 13 experiments (series 3), the excitatory component of the LES response to 5-HT was abolished by ketanserin (2.5 mg/kg i.v.) , after which only relaxation occurred. Both 5-HT2 and 5-HT3 antagonists in combination abolished all effects of 5-HT on LESP. Atropine (400 micrograms/kg i.v., n = 7) had no effect on 5-HT-induced LES responses.(ABSTRACT TRUNCATED AT 250 WORDS)

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
Keyword(s):  
Paraventricular Nucleus ◽  
Wistar Rats ◽  
Arcuate Nucleus ◽  
Chemical Stimulation ◽  
Nucleus Ambiguus ◽  
Glycine Receptors ◽  
Inhibitory Neurotransmitters ◽  
Hypothalamic Arcuate Nucleus ◽  
Male Wistar Rats ◽  
Stimulation Of

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.

scholarly journals Stimulation of the hypothalamic arcuate nucleus increases brown adipose tissue nerve activity via hypothalamic paraventricular and dorsomedial nuclei

2016 ◽  
Vol 311 (2) ◽  
pp. H433-H444 ◽  
Author(s):  
Vineet C. Chitravanshi ◽  
Kazumi Kawabe ◽  
Hreday N. Sapru
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Arcuate Nucleus ◽  
Glutamate Transporter ◽  
Nerve Activity ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Hypothalamic Arcuate Nucleus ◽  
Male Wistar Rats ◽  
Stimulation Of

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.

Role of summation of afferent input in cardiovascular reflexes from splanchnic nerve stimulation

1996 ◽  
Vol 270 (3) ◽  
pp. H849-H856 ◽  
Author(s):  
H. L. Pan ◽  
Z. B. Zeisse ◽  
J. C. Longhurst
Keyword(s):  
Electrical Stimulation ◽  
Cardiovascular Responses ◽  
Splanchnic Nerve ◽  
Afferent Input ◽  
Sympathetic Chain ◽  
Cardiovascular Reflexes ◽  
C Fibers ◽  
Greater Splanchnic Nerve ◽  
The Right

Stimulation of abdominal sympathetic visceral afferents reflexly excites the cardiovascular system. The present study examined the role of summation of afferent input in this reflex. Single-unit activity of A delta- and C-fiber afferents was recorded from the right thoracic sympathetic chain in anesthetized cats to determine the relationship between intensities of electrical stimulation and the types of nerve fibers within the right greater splanchnic nerve. The differential effect of cooling on A delta- and C-fiber axons in the sympathetic chain also was examined by recording single-unit afferent activity. Reflex cardiovascular responses were induced by electrical stimulation of the central cut end of the right greater splanchnic nerve. We observed that the numbers of A delta and C fibers activated by electrical stimulation were proportional to the intensity of stimulation. However, neither local cooling nor intensity of stimulation provided a means to separate A delta and C fibers contained in the sympathetic chain. The results demonstrate that the magnitude of excitatory cardiovascular reflexes is frequency dependent and is related directly to intensity of electrical stimulation, suggesting that both adequate discharge frequency of the afferent and sufficient numbers of afferents recruited are crucial factors for full expression of reflex cardiovascular responses.

scholarly journals Activation of hypothalamic AgRP and POMC neurons evokes disparate sympathetic and cardiovascular responses

2020 ◽  
Vol 319 (5) ◽  
pp. H1069-H1077 ◽  
Author(s):  
Jingwei Jiang ◽  
Donald A. Morgan ◽  
Huxing Cui ◽  
Kamal Rahmouni
Keyword(s):  
Blood Pressure ◽  
Arcuate Nucleus ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Melanocortin System ◽  
Physiological Processes ◽  
Essential Components ◽  
Hypothalamic Arcuate Nucleus ◽  
Chronic Activation ◽  
Two Populations

Agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons of the arcuate nucleus are essential components of the brain melanocortin system that controls various physiological processes. Here, we tested the metabolic and cardiovascular effects of direct activation of these two populations of neurons. Our findings show that, in addition to stimulation of food intake, chemogenetic mediated activation of hypothalamic arcuate nucleus AgRP, but not POMC, neurons reduce renal sympathetic traffic. Despite this, chronic activation of AgRP neurons increased blood pressure. However, chronic activation of POMC neurons led to a significant reduction in blood pressure. Our findings highlight the importance of arcuate nucleus AgRP and POMC neuronal activity in autonomic and cardiovascular regulation.

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