Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons

2003 ◽  
Vol 284 (5) ◽  
pp. R1340-R1353 ◽  
Author(s):  
Karen L. Barnes ◽  
Dannette M. DeWeese ◽  
Michael C. Andresen

Femtomole doses of angiotensin (ANG) II microinjected into nucleus tractus solitarii (nTS) decrease blood pressure and heart rate, mimicking activation of the baroreflex, whereas higher doses depress this reflex. ANG II might generate cardioinhibitory responses by augmenting cardiovascular afferent synaptic transmission onto nTS neurons. Intracellular recordings were obtained from 99 dorsal medial nTS region neurons in rat medulla horizontal slices to investigate whether ANG II modulated short-latency excitatory postsynaptic potentials (EPSPs) evoked by solitary tract (TS) stimulation. ANG II (200 fmol) increased TS-evoked EPSP amplitudes 20–200% with minimal membrane depolarization in 12 neurons excited by ANG II and glutamate, but not substance P ( group A). Blockade of non- N-methyl-d-aspartate receptors eliminated TS-evoked EPSPs and responses to ANG II. ANG II did not alter TS-evoked EPSPs in 14 other neurons depolarized substantially by ANG II and substance P ( group B). ANG II appeared to selectively augment presynaptic sensory transmission in one class of nTS neurons but had only postsynaptic effects on another group of cells. Thus ANG II is likely to modulate cardiovascular function by more than one nTS neuronal pathway.

1996 ◽  
Vol 75 (6) ◽  
pp. 2220-2228 ◽  
Author(s):  
L. Qu ◽  
A. J. McQueeney ◽  
K. L. Barnes

1. Microinjection of angiotensin (Ang) II or substance P (SP) into the medial nucleus tractus solitarii (nTS) produces similar decreases in arterial pressure and heart rate. We previously reported that some medial nTS neurons responsive to SP were also excited by Ang II, and that Ang II increased the release of SP from medulla slices. Both electrophysiological and anatomic data suggest that the cardiovascular effects of these peptides may be mediated by a common neuronal pathway consisting of SP-containing vagal afferent fibers with presynaptic Ang II receptors that innervate medial nTS neurons with SP receptors. To evaluate the validity of this model, we established the presynaptic or postsynaptic location of the receptors for Ang II and SP that mediate excitation of medial nTS neurons by determining the capacity of each peptide to activate the cell before and after blocking synaptic transmission in rat dorsal medulla slices. 2. Extracellular recordings were obtained from 55 medial nTS neurons responsive to Ang II or SP in 400-microns horizontal slices of the dorsal medulla. Neuronal excitation by Ang II and SP was tested before, during, and after reversal of synaptic blockade with low-Ca2+ (0.2 mM), high Mg2+ (5 mM) artificial cerebrospinal fluid (aCSF). Elimination of synaptically evoked short latency responses of the neuron to current pulses applied to afferent fibers in the solitary tract (TS) documented blockade of synaptic transmission by low-Ca2+ aCSF. In most cases, the basal firing rate of the cell increased slowly during perfusion with low-Ca2+ aCSF and stabilized after approximately 30 min at a higher level of spontaneous activity. Responses to the peptides and TS stimulation were also documented after synaptic blockade had been reversed by adding aCSF containing 2-mM Ca2+. 3. Of the 55 medial nTS neurons, 41 were responsive to Ang II; whereas, 50 of the 55 cells were responsive to SP. The neurons were divided into three subgroups on the basis of their responsiveness to Ang II and SP. Although most neurons were responsive to both Ang II and SP (n = 36), five other cells were excited only by Ang II, and 14 neurons were activated only by SP. Of the 55 neurons, 26 were also responsive to L-glutamate: 14 of 17 cells responsive to both Ang II and SP, all 5 neurons excited by Ang II but not by SP, and 7 of 10 neurons responsive only to SP were also excited by L-glutamate. The latency of the action potentials evoked by TS stimulation was much shorter in those neurons responsive only to Ang II (3.6 ms) than in cells excited by both Ang II and SP (6.8 ms) or responsive only to SP (7.4 ms). 4. In 21 of the 36 medial nTS neurons responsive to both Ang II and SP, Ang II continued to excite the cell when synaptic responses to TS stimulation were prevented by low-Ca2+ aCSF, but had no effect on the firing rate of the other 15 neurons during synaptic blockade. Excitation induced by Ang II was also prevented in two of the five medial nTS neurons responsive only to Ang II when synaptic transmission in the slice was blocked. Low-Ca2+ aCSF failed to prevent excitation by SP or L-glutamate in all medial nTS cells responsive to these agonists (n = 50 and n = 26, respectively). In contrast to these observations in medial nTS neurons, Ang II-induced excitation was not altered during synaptic blockade in any of the six dmnX cells studied. No responses to SP or L-glutamate were blocked in dmnX neurons, as also seen in the medial nTS. 5. When all medial nTS neurons responsive to Ang II were examined, the latencies of the response to TS stimulation were significantly shorter in those neurons with presynaptic Ang II receptors than in the group of cells with postsynaptic receptors. In addition, neurons with presynaptic Ang II receptors were distributed differently within the medial nTS than cells with postsynaptic Ang II receptors.(ABSTRACT TRUNCATED)


2011 ◽  
Vol 26 (6) ◽  
pp. 508-513 ◽  
Author(s):  
Patrícia Gomes da Silva ◽  
Daniele Cristina Cataneo ◽  
Fernanda Leite ◽  
Erica Nishida Hasimoto ◽  
Guilherme Antonio Moreira de Barros

PURPOSE: To compare analgesia traditionally used for thoracic sympathectomy to intrapleural ropivacaine injection in two different doses. METHODS: Twenty-four patients were divided into three similar groups, and all of them received intravenous dipyrone. Group A received intravenous tramadol and intrapleural injection of saline solution. Group B received intrapleural injection of 0.33% ropivacaine, and Group C 0.5% ropivacaine. The following aspects were analyzed: inspiratory capacity, respiratory rate and pain. Pain was evaluated in the immediate postoperative period by means of the visual analog scale and over a one-week period. RESULTS: In Groups A and B, reduced inspiratory capacity was observed in the postoperative period. In the first postoperative 12 hours, only 12.5% of the patients in Groups B and C showed intense pain as compared to 25% in Group A. In the subsequent week, only one patient in Group A showed mild pain while the remainder reported intense pain. In Group B, half of the patients showed intense pain, and in Group C, only one presented intense pain. CONCLUSION: Intrapleural analgesia with ropivacaine resulted in less pain in the late postoperative period with better analgesic outcomes in higher doses, providing a better ventilatory pattern.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Sadaf ◽  
Imrana Tanvir ◽  
...  

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as “+3,” was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as “+2” (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining “+1” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.


2020 ◽  
Vol 27 (12) ◽  
pp. 2648-2655
Author(s):  
Fahad Farooq ◽  
Gurdeep Singh ◽  
Farooq Ahmad ◽  
Faizan Farooq ◽  
Faiq Farooq ◽  
...  

Objective: This present study is design to assess the efficacy and frequency of side effects with a newer anti-epileptic agent levertiracetum while comparing an older anti-epileptic, Sodium Valproate, in the patients with generalized tonic colonic epilepsy. Material & Methods: Patients with GTC epilepsy had been allocated in two groups, A and B, Group A was given Sodium valproate while group B was given levertiracetum. Study Design: Randomized Control Trial. Setting: Fatima Memorial Hospital, Lahore and Allied Hospital, Faisalabad. Period: December, 2017 to December, 2018. Results: Seventy five subjects were taking levertiracetum from three months out of which 56(74.7%)were seizures free, 15(20%) were seizure free on higher dose,6(8%) were with dizziness ,vertigo and 9(12%) were with somnolence. Fifty-four individuals were seizures free with normal dose of sodium valproate from last 3 months, and 16(21%) were seizures free on higher doses among which 53(70%) were with side effects of weight gain and 69(92%) were with hand tremors and this was the most prominent side effects among individuals who were taking sodium valproate. Conclusion: Generalized tonic colonic epilepsy is one of the most common forms of epilepsy and with the advent of newer anti-epileptic drugs like levertiracetum, such seizures can be controlled in with lesser side effects as compared to older antiepileptic agent Sodium Valproate.


2020 ◽  
Author(s):  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Imrana Tanvir ◽  
Rizwan Ullah Khan ◽  
...  

AbstractTo evaluate the expression and Immunolocalization of Substance P (SP)/ Neurokinin-1 Receptor (NK-1R) in Breast Carcinoma (BC) patients and it’s association with routine proliferative markers (ER, PR, HER2/ neu and Ki-67).MethodsA cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (Grade III), 8 of group B (Grade II) and only 3 cases of group C (Grade I). Age range comprised of patients from 20-80 years and the mean age of patients was 45.74 years. HE, ER, PR, HER2 and Ki-67 staining was performed as routine biomarkers. Samples were then processed for immunomarkers study of Substance P and NK-1R immunohistochemistry was performed for few cases.Results14/23 cases (61%) of group A, 7/8 cases (88%) of group B and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥ 10% tumors cells), labeled as “3+”, was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) case of group B. Moderate staining labelled as “2+” (in ≥ 10% tumor cells) was observed in 3/14 (21.4%) cases of group A, 4/8 (50%) cases of group B. weak positive staining “1+” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B and all 2/2 (100%) cases of group C.ConclusionsSP and NK-1R is overexpressed in breast carcinomas and there is significant association between grade of tumor and their overexpression. It may serve as a novel biomarker for grading of BC. We also suggest that NK-1R antagonists as a potential therapeutic strategy to inhibit and manage BC.Key PointsImmunohistochemical expression of Substance P and Neurokinin 1 Receptor in breast carcinoma tissue was evaluatedIt was strongly expressed in grade III, with maximum intensityIt may be investigated further for its role as prognostic and diagnostic markerTherapeutic potential of Neurokinin-1 Receptor antagonists must be explored


2003 ◽  
Vol 148 (5) ◽  
pp. 515-518 ◽  
Author(s):  
G Radetti ◽  
F Buzi ◽  
C Paganini ◽  
A Pilotta ◽  
B Felappi

OBJECTIVE: Treatment of GH-deficient (GHD) children with higher doses of recombinant human GH (rhGH) than conventional ones has been reported to result in higher growth velocity and increased final height. These findings, however, were observed by comparing large but heterogeneous groups of children. We wanted to verify whether the same results could be obtained in two groups of appropriately well-matched children with isolated GHD treated with high vs conventional doses of rhGH. METHODS: Out of two cohorts of GHD children, cohort A (on a weekly rhGH dose of 0.3 mg/kg body weight) and cohort B (on a weekly rhGH dose of 0.15 mg/kg body weight), we selected two groups, each including 13 patients, who before treatment were matched for age, sex and height standard deviation score (SDS). They were followed up until final height. RESULTS: Final height SDS was significantly higher in group A (-0.45+/-0.36 (s.d.) vs -1.07+/-0.7; P=0.008), as well as height gain SDS (1.81+/-0.58 vs 1.23+/-0.62; P=0.002). The difference between final height SDS and target height SDS was positive only in group A and significantly higher in group A than in group B (0.33+/-0.51 vs -0.46+/-0.7; P=0.01). Glucose tolerance was always normal in the group treated with higher doses. CONCLUSION: The final height of children treated with higher doses of rhGH is increased, also in relation to their genetic target. The economical burden of this choice of treatment, however, has to be taken into account when evaluating the results.


2008 ◽  
Vol 295 (5) ◽  
pp. H2032-H2042 ◽  
Author(s):  
Michael C. Andresen ◽  
James H. Peters

Cranial nerve visceral afferents enter the brain stem to synapse on neurons within the solitary tract nucleus (NTS). The broad heterogeneity of both visceral afferents and NTS neurons makes understanding afferent synaptic transmission particularly challenging. To study a specific subgroup of second-order neurons in medial NTS, we anterogradely labeled arterial baroreceptor afferents of the aortic depressor nerve (ADN) with lipophilic fluorescent tracer (i.e., ADN+) and measured synaptic responses to solitary tract (ST) activation recorded from dye-identified neurons in medial NTS in horizontal brain stem slices. Every ADN+ NTS neuron received constant-latency ST-evoked excitatory postsynaptic currents (EPSCs) (jitter <192 μs, SD of latency). Stimulus-recruitment profiles showed single thresholds and no suprathreshold recruitment, findings consistent with EPSCs arising from a single, branched afferent axon. Frequency-dependent depression of ADN+ EPSCs averaged ∼70% for five shocks at 50 Hz, but single-shock failure rates did not exceed 4%. Whether adjacent ADN− or those from unlabeled animals, other second-order NTS neurons (jitters <200 μs) had ST transmission properties indistinguishable from ADN+. Capsaicin (CAP; 100 nM) blocked ST transmission in some neurons. CAP-sensitive ST-EPSCs were smaller and failed over five times more frequently than CAP-resistant responses, whether ADN+ or from unlabeled animals. Variance-mean analysis of ST-EPSCs suggested uniformly high probabilities for quantal glutamate release across second-order neurons. While amplitude differences may reflect different numbers of contacts, higher frequency-dependent failure rates in CAP-sensitive ST-EPSCs may arise from subtype-specific differences in afferent axon properties. Thus afferent transmission within medial NTS differed by axon class (e.g., CAP sensitive) but was indistinguishable by source of axon (e.g., baroreceptor vs. nonbaroreceptor).


2000 ◽  
Vol 279 (1) ◽  
pp. R239-R247 ◽  
Author(s):  
Ann M. Schreihofer ◽  
Edward M. Stricker ◽  
Alan F. Sved

Rats with chronic nucleus of the solitary tract lesions (NTS-X) drink water and release vasopressin (VP) in response to reduced blood volume despite an absence of neural signals from cardiac and arterial baroreceptors. The present study determined whether rats with NTS-X have a greater sensitivity to circulating ANG II, which may contribute to the drinking and VP responses to hypovolemia. In conscious control rats and rats with NTS-X, ANG II was infused intravenously for 1 h at 10, 100, or 250 ng · kg−1 · min−1. At the two higher doses, ANG II stimulated more water intake with a shorter latency to drink in rats with NTS-X than in control rats. In contrast, infusion of ANG II produced comparable increases in plasma VP in the two groups. At the two higher doses, ANG II produced an enhanced increase in arterial pressure (AP) in rats with NTS-X, and the bradycardia seen in control rats was reversed to a tachycardia. Infusion of hypertonic saline, which did not alter AP or heart rate, produced comparable drinking and VP release in the two groups. These results demonstrate that chronic NTS-X increases the dipsogenic response of rats to systemic ANG II but has no effect on ANG II-induced VP release or the osmotic stimulation of these responses.


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