Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract

2003 ◽  
Vol 284 (4) ◽  
pp. H1369-H1377 ◽  
Author(s):  
Cleusa V. R. de Oliveira ◽  
M. Patricia Rosas-Arellano ◽  
L. Pastor Solano-Flores ◽  
John Ciriello
Keyword(s):  
Cardiovascular Effects ◽  
Receptor Blocker ◽  
Vagal Activity ◽  
Solitary Tract ◽  
Neuronal Circuits ◽  
Reflex Bradycardia ◽  
Male Wistar Rats ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Hypocretin 1

Experiments were done in male Wistar rats to investigate the effects of microinjection of hypocretin-1 (Hcrt-1) into the nucleus of the solitary tract (NTS) on mean arterial pressure (MAP), heart rate (HR), and the baroreflex. In the first series, the distribution of Hcrt-1-like immunoreactivity (Ir) was mapped within the region of NTS. Hcrt-1 Ir was found throughout the NTS region, predominantly within the caudal dorsolateral (Slt), medial (Sm), and interstitial subnuclei of the NTS. In the second series, in α-chloralose or urethane-anesthetized rats, microinjection of Hcrt-1 (0.5–5 pmol) into the caudal NTS elicited a dose-dependent decrease in MAP and HR. A mapping of the caudal NTS region showed that the largest depressor and bradycardia responses elicited by Hcrt-1 were from sites in the Slt and Sm. In addition, doses >2.5 pmol at a small number of sites localized to the caudal commissural nucleus of NTS elicited pressor and tachycardia responses. Intravenous administration of the muscarinic receptor blocker atropine methyl bromide abolished the bradycardia response and attenuated the depressor response, whereas subsequent administration of the nicotinic receptor blocker hexamethonium bromide abolished the remaining MAP response. Finally, microinjection of Hcrt-1 into the NTS significantly potentiated the reflex bradycardia to activation of arterial baroreceptors as a result of increasing MAP by systemic injections of phenylephrine (2–4 μg/kg). These results suggest that Hcrt-1 in the NTS activates neuronal circuits that increases vagal activity to the heart, inhibits sympathetic activity to the heart and vasculature, and alters the excitability of NTS neuronal circuits that reflexly control the circulation.

Cardiovascular effects of microinjection of low doses of serotonin into the NTS of unanesthetized rats

1997 ◽  
Vol 272 (4) ◽  
pp. R1135-R1142 ◽  
Author(s):  
J. C. Callera ◽  
L. G. Bonagamba ◽  
C. Sevoz ◽  
R. Laguzzi ◽  
B. H. Machado
Keyword(s):  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Cardiovascular Reflexes ◽  
Low Doses ◽  
Reflex Bradycardia ◽  
Baseline Values ◽  
Dose Dependent Decrease ◽  
Baroreceptor Activation ◽  
Dose Dependent

In the present study, we analyzed in conscious rats the effects of microinjections of serotonin (5-HT; pmol range) into the nucleus of the solitary tract (NTS) on basal mean arterial pressure (MAP) and heart rate (HR) and also on the reflex bradycardia induced by the activation of the baro- and chemoreflex evaluated 1 min after 5-HT microinjection into the NTS. The data show that unilateral microinjection of 5-HT in the picomolar range into the NTS of unanesthetized rats produced a dose-dependent decrease in MAP and HR, which was blocked by previous microinjection of ketanserin (250 pmol/50 nl) into the NTS. The changes in MAP and HR induced by 5-HT were of very short duration, with a return to baseline values a few seconds later. The cardiovascular responses to baro- or chemoreflex activation 1 min after 5-HT microinjection into the NTS did not differ from the control, indicating that low doses of 5-HT produced no effect on the cardiovascular reflexes tested at that time. The present data show that, as also observed in anesthetized rats, the microinjection of picomolar doses of 5-HT into the NTS elicits the typical cardiovascular responses to baroreceptor activation. These effects, hypotension and bradycardia, seem to be mediated by 5-HT2 receptors because both were blocked by a selective 5-HT2 receptor antagonist. However, since microinjection of 5-HT (1 pmol) into the NTS produced no changes in the cardiovascular responses to the baro- and chemoreflex activated 1 min later, the role of 5-HT2 receptors in the processing of the cardiovascular afferent messages in the NTS remains to be elucidated.

scholarly journals Toxicological assessment of the methanolic leaf extract of Bridelia ferrugelia

2018 ◽  
Vol 7 (5) ◽  
pp. 419-424
Author(s):  
Abiodun Olusoji Owoade ◽  
◽  
Adewale Adetutu ◽  
Augustine Ikhueoya Airaodion ◽  
Olufemi Ogundeji Ogundipe ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Leaf Extract ◽  
Blood Lipids ◽  
Lipid Levels ◽  
Toxicological Evaluation ◽  
Toxicological Assessment ◽  
Acute Group ◽  
Male Wistar Rats ◽  
Dose Dependent Decrease ◽  
Dose Dependent

This study evaluated the acute and subacute toxicity effects of Bridelia ferrugelia leaf extract. Observation of the acute group showed that LD50 of the extract is greater than 2000 mg/kg. The subacute investigation was determined by administering 200 mg/kg, 400 mg/kg and 600 mg/kg of the methanolic leaf extract to male Wistar rats for 28 days with distilled water as a control. Haematological and biochemical parameters, as well as lipid levels of vital organs, were examined. Toxicological evaluation of the extract did not produce any significant change in haematological and biochemical parameters in rats. In addition, blood lipids levels were not significantly affected, while dyslipidaemia effect observed in some vital organs were found to be nonlipotoxic. Administration of Bridelia ferrugelia at a dose of 200, 400 and 600 mg/kg for 28 days resulted in reduction of cardiac cholesterol level by 37.16%, 39.36% and 17.64% respectively, reduction of pulmonary cholesterol by 22.17%, 28.08% and 6.24 % respectively and dose-dependent decrease in pulmonary triglyceride level by 16.17, 29.14 and 54.25% respectively. This study indicates that Bridelia ferrugelia extract administered at 200, 400 and 600 mg/kg did not show any toxic effect on the parameters investigated in rats. Thus, the extract can be considered safe when administered orally

Cardiac effects of hypocretin-1 in nucleus ambiguus

2003 ◽  
Vol 284 (6) ◽  
pp. R1611-R1620 ◽  
Author(s):  
John Ciriello ◽  
Cleusa V. R. de Oliveira
Keyword(s):  
Wistar Rats ◽  
Baroreceptor Reflex ◽  
Nucleus Ambiguus ◽  
Medullary Reticular Formation ◽  
Reflex Bradycardia ◽  
Male Wistar Rats ◽  
Series Of Experiments ◽  
Neuronal Systems ◽  
Direct Change ◽  
Hypocretin 1

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.

scholarly journals The Cardiovascular Effects of Central Hydrogen Sulfide Are Related to KATP Channels Activation

2011 ◽  
pp. 729-738 ◽  
Author(s):  
W.-Q. LIU ◽  
C. CHAI ◽  
X.-Y. LI ◽  
W.-J. YUAN ◽  
W.-Z. WANG ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hydrogen Sulfide ◽  
Katp Channel ◽  
Channel Blocker ◽  
Cardiovascular Effects ◽  
Katp Channels ◽  
Channel Activation ◽  
The Central Nervous System ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Hydrogen sulfide (H2S), an endogenous “gasotransmitter”, exists in the central nervous system. However, the central cardiovascular effects of endogenous H2S are not fully determined. The present study was designed to investigate the central cardiovascular effects and its possible mechanism in anesthetized rats. Intracerebroventricular (icv) injection of NaHS (0.17~17 μg) produced a significant and dose-dependent decrease in blood pressure (BP) and heart rate (HR) (P<0.05) compared to control. The higher dose of NaHS (17 μg, n=6) decreased BP and HR quickly of rats and 2 of them died of respiratory paralyse. Icv injection of the cystathionine beta-synthetase (CBS) activator s-adenosyl-L-methionine (SAM, 26 μg) also produced a significant hypotension and bradycardia, which were similar to the results of icv injection of NaHS. Furthermore, the hypotension and bradycardia induced by icv NaHS were effectively attenuated by pretreatment with the KATP channel blocker glibenclamide but not with the CBS inhibitor hydroxylamine. The present study suggests that icv injection of NaHS produces hypotension and bradycardia, which is dependent on the KATP channel activation.

Is Substance P the Transmitter at the First Synapse of the Baroreceptor Reflex in Rats and Cats?

1980 ◽  
Vol 59 (s6) ◽  
pp. 295s-297s ◽  
Author(s):  
G. Haeusler ◽  
R. Osterwalder
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Substance P ◽  
Cardiovascular Effects ◽  
Baroreceptor Reflex ◽  
Solitary Tract ◽  
Anaesthetized Rats ◽  
Contrast Exposure ◽  
Brain Ventricle ◽  
Dose Dependent

1. Substance P, injected into a lateral brain ventricle of urethane-anaesthetized rats, caused dose-dependent increases in blood pressure and heart rate. 2. By contrast, exposure of the obex region of the medulla oblongata to pieces of filter paper soaked in substance P-containing solution resulted in falls of blood pressure and heart rate in both rats and cats. 3. A more precise application of substance P to the first synapse of the baroreceptor reflex by micro-injection into defined areas of the nucleus of the solitary tract also led to an activation of the baroreceptor reflex. 4. Capsaicin, which is known to release substance P from primary afferents, mimicked the sympatho-inhibitory and cardiovascular effects of substance P when applied locally to the nucleus of the solitary tract. 5. The results are compatible with a transmitter or neuromodulatory role for substance P at the first synapse of the baroreceptor reflex.

Mechanisms of angiotensin-induced hypotension and bradycardia in the medial solitary tract nucleus

1994 ◽  
Vol 267 (1) ◽  
pp. H259-H266 ◽  
Author(s):  
J. E. Fow ◽  
D. B. Averill ◽  
K. L. Barnes
Keyword(s):  
Cardiovascular Effects ◽  
Receptor Subtype ◽  
Motor Nucleus ◽  
Ang Ii ◽  
Solitary Tract ◽  
Induced Hypotension ◽  
Medial Nucleus ◽  
Dorsal Motor Nucleus ◽  
At1 Antagonist ◽  
Dose Dependent

The selective angiotensin (ANG) II antagonists losartan (AT1) and CGP-42112A (AT2) were used to determine the receptor subtype and neuronal pathways that mediate the hypotension and bradycardia produced by 200 fmol of ANG II microinjected into the dorsal medial nucleus tractus solitarii (NTS) or dorsal motor nucleus of the vagus (dmnX) in anesthetized rats. At dorsal medial NTS sites (0.3 mm below the surface) where L-glutamate microinjections produced maximal decreases in mean arterial pressure (MAP) and heart rate (HR), ANG II (200 fmol, 50 nl, n = 16) elicited hypotension (-22 +/- 1 mmHg) and bradycardia (-26 +/- 2 beats/min). Although L-glutamate also suppressed respiration, ANG II injections in the medial NTS did not alter respiration. Losartan injected at the medial NTS site caused a dose-dependent reduction of ANG II-induced decreases in MAP and HR. At 2 pmol, the AT1 antagonist attenuated the response to ANG II, whereas 100 pmol abolished the effects of ANG II microinjections. In contrast, the AT2 antagonist CGP-42112A (100 pmol) had no effect on the responses to ANG II. Neither ANG II antagonist altered the cardiovascular effects of L-glutamate injections. Losartan injected into the dmnX blocked hypotension and bradycardia produced by ANG II at that site but did not prevent responses to subsequent ANG II injections in the medial NTS.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Neurodynamic Influence of Hydrocortisone on Rhinencephalic and Telencephalic Brain Areas

2019 ◽  
pp. 1-7
Author(s):  
Ilochi Ogadinma ◽  
Daniel Yaro Onoja ◽  
Chuemere Arthur Nwafor
Keyword(s):  
Brain Tissue ◽  
Brain Regions ◽  
Biochemical Tests ◽  
Male Wistar Rats ◽  
Tissue Homogenates ◽  
Calcium Magnesium ◽  
Tissue Calcium ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Hydrocortisone Treatment

The neurodynamic effect of graded hydrocortisone treatment on rhinencephalic and telencephalic brain regions was studied in an experimental animal design that sampled isolated hippocampal, basal nucleic and frontal cortical brain regions of male wistar rats. Four test groups, ii to v were administered 2.5 mg, 5 mg, 7.5 mg and 10 mg respectively. The study period lasted for 6 weeks. Results were statistically analyzed and considered significantly different at a confidence interval of 95%. There was a progressive decline in olfactory response as dose of hydrocortisone treatment was increased. There was a significant dose-dependent decrease in assayed frontal cortical acetylcholine and hippocampal glutamate in brain tissue homogenates. Similar change was observed in brain tissue calcium, magnesium and sodium. For the behavioral, histological and biochemical tests conducted in this study, 6 weeks hydrocortisone treatment showed adverse manifestations from 5 mg, which was more obvious from 7.5 mg. The outcome of this study revealed a possible dose-dependent adverse effect of hydrocortisone on specific brain regions responsible for learning, memory, olfaction and psychosocial behavior.

Differences between cytokine effects in the microcirculation of the rat

1996 ◽  
Vol 271 (3) ◽  
pp. H1186-H1192 ◽  
Author(s):  
N. Baudry ◽  
C. Rasetti ◽  
E. Vicaut
Keyword(s):  
Vascular Reactivity ◽  
Thromboxane A2 ◽  
Cardiovascular Effects ◽  
Short Exposure ◽  
Thromboxane A2 Receptor ◽  
Delayed Effects ◽  
Basal Tone ◽  
Dose Dependent Decrease ◽  
Dose Dependent

We studied by in vivo microscopy in rat cremaster muscle the acute and delayed effects of short exposure to tumor necrosis factor (TNF), interleukin (IL)-1 beta, and IL-6 on basal tone and vascular reactivity of second- to fourth-order arterioles (A2-A4). A 20-min exposure to recombinant human (rh) TNF (0.1-10 ng/ml) induced a significant arteriolar vasodilation, but no significant changes in basal tone were found after exposure to the same doses of IL-1 beta. In contrast, the same exposure to IL-6 (0.1-10 ng/ml) induced a significant dose-dependent vasoconstriction (i.e., 8, 15, and 21% at 10 ng/ml in A2-A4 arterioles, respectively). This vasoconstriction was inhibited by the thromboxane A2 receptor antagonist SQ-29548. We did not find any significant effect of rhTNF or IL-6 on vascular reactivity to norepinephrine immediately after exposure to these two cytokines or 100 min after the end of the exposure. Contrastingly, a large dose-dependent decrease in reactivity to norepinephrine was found immediately after exposure to IL-1 beta and still persisted 100 min after the end of the exposure. Such a decrease was not found for the vasoconstriction in response to KCl. We conclude that, at the microvascular level, large differences exist between the three cytokines generally considered to mediate the harmful cardiovascular effects in sepsis. 1) TNF but not IL-1 beta is responsible for a vasodilatory effect, whereas the effect of IL-6 is a thromboxane A2-mediated vasoconstriction. 2) Short exposure to IL-1 beta but not to rhTNF or IL-6 diminishes the response of the arterioles to norepinephrine but not to KCl.

Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

1988 ◽  
Vol 255 (6) ◽  
pp. R1035-R1040
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
L. C. Wang ◽  
R. Rajotte
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Low Temperatures ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Exogenous Insulin ◽  
Metabolic Substrate ◽  
Endogenous Insulin ◽  
Dose Dependent Decrease ◽  
Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

scholarly journals A Reversible Shift of Driver Dependence from EGFR to Notch1 in Non-Small Cell Lung Cancer as a Cause of Resistance to Tyrosine Kinase Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2022
Author(s):  
Francesca Iommelli ◽  
Viviana De Rosa ◽  
Cristina Terlizzi ◽  
Rosa Fonti ◽  
Rosa Camerlingo ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Epithelial Mesenchymal Transition ◽  
Parental Cell ◽  
Egfr Inhibitors ◽  
Simultaneous Increase ◽  
Adherent Cells ◽  
Binding Assays ◽  
Mesenchymal Transition ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Notch1 plays a key role in epithelial-mesenchymal transition (EMT) and in the maintenance of cancer stem cells. In the present study we tested whether high levels of activated Notch1 in oncogene-driven NSCLC can induce a reversible shift of driver dependence from EGFR to Notch1, and thus causing resistance to EGFR inhibitors. Adherent cells (parental) and tumor spheres (TS) from NSCLC H1975 cells and patient-derived CD133-positive cells were tested for EGFR and Notch1 signaling cascade. The Notch1-dependent modulation of EGFR, NCID, Hes1, p53, and Sp1 were then analyzed in parental cells by binding assays with a Notch1 agonist, DLL4. TS were more resistant than parental cells to EGFR inhibitors. A strong upregulation of Notch1 and a concomitant downregulation of EGFR were observed in TS compared to parental cells. Parental cell exposure to DLL4 showed a dose-dependent decrease of EGFR and a simultaneous increase of NCID, Hes1, p53, and Sp1, along with the dislocation of Sp1 from the EGFR promoter. Furthermore, an enhanced interaction between p53 and Sp1 was observed in TS. In NSCLC cells, high levels of active Notch1 can promote a reversible shift of driver dependence from EGFR to Notch1, leading to resistance to EGFR inhibitors.

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