Fluoxetine oral treatment discloses 5-HT1D receptor as vagoinhibitor of the cardiac cholinergic neurotransmission in rat

2019 ◽  
Vol 97 (2) ◽  
pp. 90-98 ◽  
Author(s):  
Cristina López ◽  
Miriam Gómez-Roso ◽  
José Ángel García-Pedraza ◽  
María Luisa Martín ◽  
Asunción Morán ◽  
...  
Keyword(s):  
Vagal Stimulation ◽  
Oral Treatment ◽  
Inhibitory Effect ◽  
Control Group ◽  
Water Control ◽  
Fluoxetine Treatment ◽  
Pithed Rats ◽  
Cardiac Regulation ◽  
Stimulation Of

Although depression and cardiovascular diseases are related, the role of antidepressants such as fluoxetine (increasing serotonin levels) within cardiac regulation remains unclear. We aimed to determine whether fluoxetine modifies the pharmacological profile of serotonergic influence on vagal cardiac outflow. Rats were treated with fluoxetine (10 mg/kg per day; p.o.) for 14 days or equivalent volumes of drinking water (control group); then, they were pithed and prepared for vagal stimulation. Bradycardic responses were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or i.v. acetylcholine (ACh; 1, 5, and 10 μg/kg). The i.v. administration of 5-hydroxytryptamine (5-HT; 10 and 50 μg/kg) inhibited the vagally induced bradycardia. 5-CT (5-HT1/7 agonist) and L-694,247 (5-HT1D agonist) mimicked the serotonin inhibitory effect while α-methyl-5-HT (5-HT2 agonist) was devoid of any action. SB269970 (5-HT7 antagonist) did not abolish 5-CT inhibitory action on the electrically induced bradycardia. Pretreatment with LY310762 (5-HT1D antagonist) blocked the effects induced by L-694,247 and 5-CT. 5-HT and 5-CT failed to modify the bradycardia induced by exogenous ACh. Our outcomes suggest that fluoxetine treatment modifies 5-HT modulation on heart parasympathetic neurotransmission in rats, evoking inhibition of the bradycardia via prejunctional 5-HT1D in pithed rats.

The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Rna Extraction ◽  
Cell Plate ◽  
Inhibitory Effect ◽  
Control Group ◽  
Ht29 Cells ◽  
Guluronic Acid ◽  
Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;

Vagal control of pyloric resistance

1995 ◽  
Vol 269 (4) ◽  
pp. G558-G569 ◽  
Author(s):  
C. H. Malbert ◽  
C. Mathis ◽  
J. P. Laplace
Keyword(s):  
Gastric Emptying ◽  
Temporal Relationship ◽  
Vagal Stimulation ◽  
Simultaneous Recording ◽  
Nervous Control ◽  
Transpyloric Flow ◽  
Cervical Vagotomy ◽  
Vagal Efferents ◽  
Stimulation Of

Pyloric resistance is probably a major factor regulating gastric emptying of liquids, but its nervous control is unknown. The role of efferent vagal pathways in pyloric resistance was evaluated in 13 anesthetized pigs. Pyloric resistance was assessed by simultaneous recording of gastropyloroduodenal motility and transpyloric flow during gastric emptying of saline. Cervical vagotomy suppressed all antral pressure events, increased the number of pressure events localized at the pylorus, and decreased the frequency of the flow pulses (P < 0.05), without affecting either pyloric resistance or the characteristics of flow pulses. Electrical stimulation of the cervical and the thoracic vagi both decreased pyloric resistance by about 60% and increased the stroke volume of flow pulses (P < 0.05). The reduced pyloric resistance was mainly related to an alteration of the temporal relationship between flow pulses and pyloric pressure events. These results indicate that vagal efferents could provide inhibitory inputs to pyloric resistance. A reduction in pyloric resistance contributes to the increased flow rate observed during vagal stimulation.

scholarly journals Activation of angiotensin II type 2 receptor suppresses TNF-α-induced ICAM-1 via NF-кB: possible role of ACE2

2015 ◽  
Vol 309 (5) ◽  
pp. H827-H834 ◽  
Author(s):  
Liping Zhu ◽  
Oscar A. Carretero ◽  
Jiang Xu ◽  
Pamela Harding ◽  
Nithya Ramadurai ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Ang Ii ◽  
Human Coronary Artery ◽  
Activity Inhibition ◽  
Tnf Α ◽  
System Activation ◽  
Interfering Rna ◽  
Stimulation Of

ANG II type 2 receptor (AT2) and ANG I-converting enzyme 2 (ACE2) are important components of the renin-ANG system. Activation of AT2 and ACE2 reportedly counteracts proinflammatory effects of ANG II. However, the possible interaction between AT2 and ACE2 has never been established. We hypothesized that activation of AT2 increases ACE2 activity, thereby preventing TNF-α-stimulated ICAM-1 expression via inhibition of NF-κB signaling. Human coronary artery endothelial cells were pretreated with AT2 antagonist PD123319 (PD) or ACE2 inhibitor DX600 and then stimulated with TNF-α in the presence or absence of AT2 agonist CGP42112 (CGP). We found that AT2 agonist CGP increased both ACE2 protein expression and activity. This effect was blunted by AT2 antagonist PD. ICAM-1 expression was very low in untreated cells but greatly increased by TNF-α. Activation of AT2 with agonist CGP or with ANG II under concomitant AT1 antagonist reduced TNF-α-induced ICAM-1 expression, which was reversed by AT2 antagonist PD or ACE2 inhibitor DX600 or knockdown of ACE2 with small interfering RNA. AT2 activation also suppressed TNF-α-stimulated phosphorylation of inhibitory κB (p-IκB) and NF-κB activity. Inhibition of ACE2 reversed the inhibitory effect of AT2 on TNF-α-stimulated p-IκB and NF-κB activity. Our findings suggest that stimulation of AT2 reduces TNF-α-stimulated ICAM-1 expression, which is partly through ACE2-mediated inhibition of NF-κB signaling.

scholarly journals The Inhibitory Effect of WenxinKeli on H9C2 Cardiomyocytes Hypertrophy Induced by Angiotensin II through Regulating Autophagy Activity

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jie Li ◽  
Yang Li ◽  
Ying Zhang ◽  
Dan Hu ◽  
Yonghong Gao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Inhibitory Effect ◽  
Cytoskeletal Proteins ◽  
Confocal Imaging ◽  
Control Group ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
H9c2 Cardiomyocytes ◽  
Cardiomyocyte Autophagy

Objectives. We investigated the role of cardiomyocyte autophagy and its regulatory mechanisms by WenxinKeli (WXKL) in cells subjected to hypertrophy. Methods. H9C2 cardiomyocytes were divided into 8 groups. Cytoskeletal proteins as well as endogenously expressed autophagy marker proteins were studied by confocal imaging. Western blotting was used to assess the levels of light chain-3 (LC3) and mechanistic target of rapamycin (mTOR). The cell viability assay was used to detect the content of ATP. Flow cytometry was used to detect apoptotic cardiomyocytes. Results. (1) Compared with the control group, the length and width of cells in the Angiotensin II (AngII) group were significantly increased, while those in the 3-methyladenine (3-MA) and the WXKL groups were decreased. (2) Compared with AngII group, the expression of LC3 II/I protein in the 3-MA and WXKL groups was downregulated, while the expression of mTOR protein was upregulated. (3) Compared with the AngII group, the cardiomyocytes in the WXKL group showed increased ATP and decreased apoptosis rate and number of autophagosome. Conclusions. We propose a novel role of WXKL as a likely inhibitor of cardiac hypertrophy by regulation of pathological autophagy.

scholarly journals The role of interfering RNA in immune response proliferative processes regulation in experimental model of endometrial cancer associated with thyroid disease

2013 ◽  
Vol 94 (3) ◽  
pp. 340-343
Author(s):  
V M Zaporozhan ◽  
G S Maryniuk ◽  
O L Kholodkova ◽  
D U Andronov
Keyword(s):  
Dendritic Cells ◽  
Endometrial Cancer ◽  
Thyroid Disease ◽  
Tumor Tissue ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Control Group ◽  
Sirna Transfection ◽  
Guerin’S Carcinoma

Aim. To assess the proliferation and dendritic cells markers expression degree at short interference RNA (siRNA) transfection in endometrial cancer associated with experimental thyroid disease. Methods. Experiments were performed on female rats distributed to five groups: I - control group; IIA and IIIА - animals with simulated hypo-and hyperthyroidism and transplanted Guérin’s carcinoma, IIВ and IIIB - animals with simulated hypo- and hyperthyroidism and transplanted Guérin’s carcinoma in combination with siRNA transfection. Orthogonal tumor dimensions were measured starting from the 7-th day after tumor suspension inoculation. Proliferation and dendritic cells markers expression were assessed in tumor samples by immunohistochemistry after the exclusion of animals from the experiment. Results. siRNA inhibitory effect was more marked in animals with hypothyroidism, indicating an important role of thyroid hormones in regulating cell cycle controlling genes expression. Transfection of siRNA increased mature dendritic cells (CD83) expression in tumor tissue in animals with hypothyroidism and increased immature dendritic cells (CD1a) expression in tumor tissue in animals with hyperthyroidism. Conclusion. siRNA transfection inhibits the tumor cells proliferation mainly at hypothyroidism compared to hyperthyroidism.

The role of external factors in realizing of the natural progress of the child’s motor development within the first year of life

2021 ◽  
Vol 2 (3) ◽  
pp. 119-136
Author(s):  
Galina S. Lupandina-Bolotova ◽  
Aliya A. Revina ◽  
Dmitry A. Ignatov
Keyword(s):  
Nervous System ◽  
Treatment Group ◽  
Motor Skills ◽  
Motor Development ◽  
Control Group ◽  
First Year ◽  
Functional Disorders ◽  
First Year Of Life ◽  
Stimulation Of

Introduction. The development of a child in the first year of life provides the basis for their further harmonious growth. Motor development occurs in parallel with the ongoing gradual development of the nervous system. The transition to a new motor milestone is associated with the emergence of new skills; therefore, stimulation of motor development should occur in accordance with the next milestone of the nervous system development. Intervention in the natural process of the skills gaining without considering the developmental nervous system milestone leads to a change in the trajectory of motor progress of the child. Aim of the study was to assess the significance of individual elements of motor development for the function of balance and walking, as well as to identify the role of non-physiologic (contradicting motor ontogenesis) stimulation of motor skills in the evolvement of non-optimal motor patterns and impaired balance and walking function. Materials and methods. In total, 43 children aged ≥ 12 months admitted to the «Consultative Diagnostic Department» of the Federal State Autonomous Institution «National Medical Research Center for Children’s Health» of the Ministry of Health of Russia were examined within the framework of dispensary observation in the period from December 2016 to June 2019. The assessment of motor development was carried out according to the tests and questionnaires developed. The children were divided into two groups: the treatment group, in which the intervention was carried out, and the control group. Results. The frequency of realization of physiological patterns in children in the treatment group was 65.5%, and in the control group was 89.6%. The occurrence of the functional disorders of the musculoskeletal system was as follows: pathological functional kyphosis in the lumbar spine in children in the treatment group occurred in 73.1%, and in the control group in 26.9%; sitting on the sacrum occurred in 73.1% in the treatment group, and 26.9 % in the control group; impaired coordination in the treatment group occurred in 53.9%, and in 46.1% in the control group; decreased balance function in the treatment group occurred in 61.5%, and in 38.5% in the control group. Conclusion. Correct interaction with a child in the first year of life, in combination with physiological stimulation corresponding to the developmental milestones of the nervous system, allows the child to implement their motor skills in a timely manner, without disrupting the natural sequence of motor development, and minimizes the risks of functional disorders of the musculoskeletal system.

Angiotensin II attenuates myocardial interstitial acetylcholine release in response to vagal stimulation

2007 ◽  
Vol 293 (4) ◽  
pp. H2516-H2522 ◽  
Author(s):  
Toru Kawada ◽  
Toji Yamazaki ◽  
Tsuyoshi Akiyama ◽  
Meihua Li ◽  
Can Zheng ◽  
...  
Keyword(s):  
Acetylcholine Release ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Inhibitory Effect ◽  
Local Administration ◽  
Control Group ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Ach Release ◽  
Parasympathetic Ganglia

Although ANG II exerts a variety of effects on the cardiovascular system, its effects on the peripheral parasympathetic neurotransmission have only been evaluated by changes in heart rate (an effect on the sinus node). To elucidate the effect of ANG II on the parasympathetic neurotransmission in the left ventricle, we measured myocardial interstitial ACh release in response to vagal stimulation (1 ms, 10 V, 20 Hz) using cardiac microdialysis in anesthetized cats. In a control group ( n = 6), vagal stimulation increased the ACh level from 0.85 ± 0.03 to 10.7 ± 1.0 (SE) nM. Intravenous administration of ANG II at 10 μg·kg−1·h−1 suppressed the stimulation-induced ACh release to 7.5 ± 0.6 nM ( P < 0.01). In a group with pretreatment of intravenous ANG II receptor subtype 1 (AT1 receptor) blocker losartan (10 mg/kg, n = 6), ANG II was unable to inhibit the stimulation-induced ACh release (8.6 ± 1.5 vs. 8.4 ± 1.7 nM). In contrast, in a group with local administration of losartan (10 mM, n = 6) through the dialysis probe, ANG II inhibited the stimulation-induced ACh release (8.0 ± 0.8 vs. 5.8 ± 1.0 nM, P < 0.05). In conclusion, intravenous ANG II significantly inhibited the parasympathetic neurotransmission through AT1 receptors. The failure of local losartan administration to nullify the inhibitory effect of ANG II on the stimulation-induced ACh release indicates that the site of this inhibitory action is likely at parasympathetic ganglia rather than at postganglionic vagal nerve terminals.

Role of nitric oxide in gastric hyperemia induced by central vagal stimulation

1993 ◽  
Vol 264 (2) ◽  
pp. G280-G284 ◽  
Author(s):  
T. Tanaka ◽  
P. Guth ◽  
Y. Tache
Keyword(s):  
Nitric Oxide ◽  
Acid Secretion ◽  
Vagal Stimulation ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Hydrogen Gas ◽  
Hydrogen Gas Clearance ◽  
Intracisternal Injection ◽  
Stimulation Of

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on the vagal cholinergic increase in gastric mucosal blood flow (GMBF) and acid secretion induced by intracisternal injection of the thyrotropin-releasing hormone (TRH) analogue, RX 77368, were studied. GMBF and acid secretion were measured simultaneously by the hydrogen gas clearance technique and titration of gastric perfusate in urethan-anesthetized rats. RX 77368 (30 ng) injected intracisternally stimulated gastric acid secretion and GMBF for 90 and 180 min respectively. GMBF was increased from basal 63 +/- 4 to 166 +/- 14 ml.min-1.100 g-1 at 60 min postinjection. L-NAME (3 mg/kg) injected intravenously 15 min before RX 77368 completely prevented the increase in GMBF induced by the TRH analogue, whereas the acid response was not modified. The effect of L-NAME was reversed by L-arginine but not by the stereoisomer D-arginine. These results show that the increase in GMBF, but not the stimulation of acid secretion, induced by central vagal activation is mediated through a product of L-arginine-NO pathway.

scholarly journals Role of low circulating FSH concentrations in controlling the interval to emergence of the subsequent follicular wave in cattle

Reproduction ◽  
2002 ◽  
pp. 475-482 ◽  
Author(s):  
OJ Ginther ◽  
DR Bergfelt ◽  
MA Beg ◽  
K Kot
Keyword(s):  
Dosage Regimen ◽  
Treated Group ◽  
Systemic Effect ◽  
Reciprocal Relationship ◽  
Control Group ◽  
Follicular Waves ◽  
Follicular Wave ◽  
Follicle Diameter ◽  
Stimulation Of

The intervals between emergence of follicular waves 1 (first wave of an oestrous cycle) and 2, and between the associated FSH surges (surges 1 and 2), were studied in control (n = 7) and recombinant bovine (rb)FSH-treated (n = 7) heifers. The expected start of the deviation in follicle diameter between the two largest follicles of wave 1 was defined as the day on which the largest follicle reached 8.5 mm (day 0). In the control heifers, circulating concentrations of FSH decreased and oestradiol increased between day 0 and day 1.5 or day 2.0 in a reciprocal relationship. The opposite reciprocal relationship between an FSH increase and an oestradiol decrease occurred during the next 3 days. This temporal result is consistent with a negative systemic effect of oestradiol on FSH at this time. rbFSH was administered in a dosage regimen that was expected to result in a similarity between FSH surge 2 in the rbFSH-treated group and surge 2 in the control group. On average, surge 2 and wave 2 occurred approximately 2 days earlier in the rbFSH-treated group than in the control group, and characteristics of the FSH surge and follicular wave were similar (no significant differences) between groups. These results support the hypothesis that low circulating FSH concentrations after the deviation in follicle diameter control the interval to emergence of the subsequent follicular wave. However, in one of seven rbFSH-treated heifers, the largest follicle from the apparent stimulation of rbFSH reached only 5.7 mm; therefore, the possibility of involvement of additional mechanisms cannot be dismissed.

Vasopressin secretion after stimulation of abdominal vagus in rabbit: role of A1 norepinephrine neurons

1994 ◽  
Vol 266 (6) ◽  
pp. R1885-R1890 ◽  
Author(s):  
Z. J. Gieroba ◽  
W. W. Blessing
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Medulla Oblongata ◽  
Vagal Stimulation ◽  
Vagal Afferents ◽  
Neuronal Function ◽  
Plasma Vasopressin ◽  
Vasopressin Secretion ◽  
Stimulation Of

We determined whether electrical stimulation of the abdominal vagus nerve causes secretion of vasopressin in the rabbit and whether inhibition of neuronal function in the A1 region of the medulla oblongata impairs this secretion. In urethan-anesthetized rabbits, electrical stimulation of the abdominal vagus (5-min train of cathodal pulses, 0.5 ms duration, 20 Hz, 0.5-1 mA) increased plasma vasopressin from 37 +/- 8 to 133 +/- 19 pg/ml (P < 0.01, n = 11). Prior section of the cervical vagus completely prevented the increase seen with stimulation of the abdominal vagus. Injecting the inhibitory agent muscimol (1 nmol) 2 mm dorsal to the A1 area did not significantly reduce the vasopressin response to abdominal vagal stimulation. However, when muscimol was injected into the A1 area, the vagally mediated increase in plasma vasopressin was completely prevented. Our results show that stimulation of abdominal vagal afferents causes secretion of vasopressin in the rabbit via a central pathway that includes neurons in the A1 area.

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