Cardiovascular effects of angiotensin-(1-7) injected into the dorsal medulla of rats

1989 ◽  
Vol 257 (1) ◽  
pp. H324-H329 ◽  
Author(s):  
M. J. Campagnole-Santos ◽  
D. I. Diz ◽  
R. A. Santos ◽  
M. C. Khosla ◽  
K. B. Brosnihan ◽  
...  
Keyword(s):  
Cardiovascular Effects ◽  
Major Product ◽  
High Dose ◽  
Motor Nucleus ◽  
Ang Ii ◽  
Amino Terminal ◽  
Medial Nucleus ◽  
Angiotensin Peptides ◽  
Dorsal Motor Nucleus ◽  
Dorsal Medulla

The amino terminal angiotensin heptapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro [ANG-(1–7)], is the major product formed during incubation of 125I-labeled ANG I or 125I-labeled ANG II with homogenates obtained from canine dorsomedial medulla oblongata. To determine whether ANG-(1–7) has central-mediated cardiovascular effects, this heptapeptide was microinjected into the dorsal medulla of chloralose-urethan-anesthetized rats. Unilateral injections of ANG-(1-7) into the medial nucleus tractus solitarii caused depressor and bradycardic effects at doses between 0.1 and 12.5 ng. Similar hypotensive responses accompanied with bradycardia were produced by injections of ANG-(1–7) into the dorsal motor nucleus of the vagus. In both nuclei, the monophasic depressor responses elicited by ANG-(1–7) were qualitatively similar to those found with injections of ANG II. Biphasic depressor-pressor responses of variable magnitude were produced by the injection of either angiotensin peptide at a high dose (250 ng). Because ANG-(1–7) has no direct vascular or dipsogenic effects, our findings suggest important differences in the receptor requirements for vascular and neural tissue of the dorsal medulla. Moreover, the data support the concept of tissue specific formation and action of angiotensin peptides in the brain.

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)

Presynaptic or postsynaptic location of receptors for angiotensin II and substance P in the medial solitary tract nucleus

1996 ◽  
Vol 75 (6) ◽  
pp. 2220-2228 ◽  
Author(s):  
L. Qu ◽  
A. J. McQueeney ◽  
K. L. Barnes
Keyword(s):  
Substance P ◽  
Synaptic Transmission ◽  
Firing Rate ◽  
Cardiovascular Effects ◽  
Ang Ii ◽  
Solitary Tract ◽  
Medial Nucleus ◽  
Afferent Fibers ◽  
Before And After ◽  
Dorsal Medulla

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)

Aortic nerve-activated cardioinhibitory neurons and interneurons

1975 ◽  
Vol 229 (3) ◽  
pp. 783-789 ◽  
Author(s):  
J Schwaber ◽  
N Schneiderman
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Baroreceptor Reflex ◽  
Motor Nucleus ◽  
Vagus Nerves ◽  
Antidromic Activation ◽  
Medial Nucleus ◽  
Aortic Nerve ◽  
Dorsal Motor Nucleus ◽  
Stimulation Of

Unit activity evoked by electrical stimulation of the aortic and vagus nerves was recorded in the dorsal motor nucleus and nucleus solitarius of unanesthetized rabbits. Cardioinhibitory cells which showed antidromic activation to stimulation of the vagus nerve and synaptic activation to stimulation of the aortic nerve were localized in lateral dorsal motor nucleus 0.5-0.8 mm anterior of the obex. Additionally, units were found that appeared to be interneurons in the medullary pathway subserving baroreceptor reflex effects on cardioinhibitory neurons. These cells were activated by aortic, and usually vagus, nerve stimulation, appeared to be polysynaptically activated, and were located in medial nucleus solitarius rostral to the obex. Neurons reflecting a cardiac rhythm but not activated by aortic nerve stimulation were also observed.

scholarly journals The renin-angiotensin system: going beyond the classical paradigms

2019 ◽  
Vol 316 (5) ◽  
pp. H958-H970 ◽  
Author(s):  
Robson Augusto Souza Santos ◽  
Gavin Y. Oudit ◽  
Thiago Verano-Braga ◽  
Giovanni Canta ◽  
Ulrike Muscha Steckelings ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Protective Effects ◽  
Ang Ii ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Amino Terminal ◽  
Angiotensin Peptides ◽  
Protective Actions

Thirty years ago, a novel axis of the renin-angiotensin system (RAS) was unveiled by the discovery of angiotensin-(1−7) [ANG-(1−7)] generation in vivo. Later, angiotensin-converting enzyme 2 (ACE2) was shown to be the main mediator of this reaction, and Mas was found to be the receptor for the heptapeptide. The functional analysis of this novel axis of the RAS that followed its discovery revealed numerous protective actions in particular for cardiovascular diseases. In parallel, similar protective actions were also described for one of the two receptors of ANG II, the ANG II type 2 receptor (AT2R), in contrast to the other, the ANG II type 1 receptor (AT1R), which mediates deleterious actions of this peptide, e.g., in the setting of cardiovascular disease. Very recently, another branch of the RAS was discovered, based on angiotensin peptides in which the amino-terminal aspartate was replaced by alanine, the alatensins. Ala-ANG-(1−7) or alamandine was shown to interact with Mas-related G protein-coupled receptor D, and the first functional data indicated that this peptide also exerts protective effects in the cardiovascular system. This review summarizes the presentations given at the International Union of Physiological Sciences Congress in Rio de Janeiro, Brazil, in 2017, during the symposium entitled “The Renin-Angiotensin System: Going Beyond the Classical Paradigms,” in which the signaling and physiological actions of ANG-(1−7), ACE2, AT2R, and alatensins were reported (with a focus on noncentral nervous system-related tissues) and the therapeutic opportunities based on these findings were discussed.

Cardiovascular responses to microinjection of ANF into dorsal medulla of rats

1988 ◽  
Vol 255 (1) ◽  
pp. R182-R187 ◽  
Author(s):  
D. J. McKitrick ◽  
F. R. Calaresu
Keyword(s):  
Area Postrema ◽  
Cardiovascular Responses ◽  
Significant Decline ◽  
Medial Longitudinal Fasciculus ◽  
Hypoglossal Nucleus ◽  
Cardiovascular Reflexes ◽  
Motor Nucleus ◽  
Cuneate Nucleus ◽  
Dorsal Motor Nucleus ◽  
Dorsal Medulla

Atrial natriuretic factor (ANF) has been suggested as a putative neurotransmitter in central pathways involved in the control of the cardiovascular system. To investigate this possibility, 50 nl of 10(-7) M ANF were microinjected into discrete sites in the nucleus of the tractus solitarius (NTS) where baro- and chemoreceptor afferents terminate. Injections into 36 of a total of 66 sites in the NTS of paralyzed artificially ventilated Wistar rats under urethan anesthesia were found to produce a significant decline in heart rate [HR; -9.2 +/- 2.9 (SE) beats/min, P less than 0.05] and mean arterial pressure [MAP; -11.1 +/- 1.2 (SE) mmHg, P less than 0.01]. Similar responses were also present in anesthetized animals breathing spontaneously. Microinjection of an inactive peptide analogue or of saline did not produce cardiovascular changes. It was also found that ANF injection into the cuneate nucleus (20 of 38 sites) and the spinal trigeminal complex (28 of 42 sites) produced a decrease in MAP and HR that were of the same magnitude as those seen in the NTS. Injections of ANF into the medial longitudinal fasciculus (n = 22), hypoglossal nucleus (n = 9), area postrema (n = 16), and dorsal motor nucleus of the vagus (n = 11) did not change HR or MAP. These results suggest that ANF may serve as a neurotransmitter involved in cardiovascular reflexes mediated by specific nuclei in the dorsal medulla.

Localization of sites within dorsal motor nucleus of vagus that affect gastric motility

1985 ◽  
Vol 249 (1) ◽  
pp. G73-G84 ◽  
Author(s):  
F. D. Pagani ◽  
W. P. Norman ◽  
D. K. Kasbekar ◽  
R. A. Gillis
Keyword(s):  
Heart Rate ◽  
Electrical Stimulation ◽  
Arterial Pressure ◽  
Gastric Motility ◽  
Motor Nucleus ◽  
Fast Blue ◽  
Medial Nucleus ◽  
Dorsal Motor Nucleus ◽  
Propantheline Bromide ◽  
Stimulation Of

The purpose of our study was to determine the localization of sites within the dorsal motor nucleus of the vagus (DMV) of the cat that when stimulated would increase gastric motility. To do this, two types of experiments were performed. First, the retrograde tracer fast blue was injected into the antrum and pylorus, and labeled neurons in the DMV were identified. Second, electrical stimulation was performed in areas of the DMV labeled with fast blue as well as in nearby areas with no labeling while monitoring gastric motility, arterial pressure, and heart rate. Results from the first type of studies revealed that peak labeling in the DMV occurred between 0.56 and 1.56 mm rostral to obex. Electrical stimulation in this area using 100 microA, 0.2 ms duration pulses, and 50 Hz resulted in increases in antral and pyloric contractions in 20 animals. The magnitude of pyloric and antral responses elicited by stimulation of the DMV generally correlated to the number of cell bodies labeled with fast blue within the DMV. No changes in arterial pressure occurred, and only a slight (-4%) decrease in heart rate was observed. Maximal increases in motility occurred with 20 Hz (antrum) or 100 Hz (pylorus). These increases in motility were maintained even at 200- and 400-Hz stimulation. Ipsilateral vagotomy or pretreatment with propantheline bromide prevented the increases in gastric motility produced by electrical stimulation of the DMV. Electrical stimulation of more rostral sites in the DMV, the medial nucleus of the solitary tract (NTS), and an area within 1.0 mm medial to the DMV resulted in attenuated or no motility responses. Stimulation of the medial nucleus of the NTS did result in pronounced slowing in heart rate (-61 +/- 21 beats/min). These results suggest that there is a localization of a “stomach area” within the DMV and that electrical stimulation of this area results in gastric motility responses that are mediated by vagal fibers projecting directly to the stomach. In addition, electrical stimulation of the DMV results in selective effects on the gastrointestinal tract in that no pronounced changes in heart rate and arterial pressure occur.

scholarly journals Effects of Electrical Stimulation at Different Locations in the Central Nucleus of Amygdala on Gastric Motility and Spike Activity

2016 ◽  
pp. 693-700 ◽  
Author(s):  
F. HE ◽  
H.-B. AI
Keyword(s):  
Electrical Stimulation ◽  
Gastric Motility ◽  
Spike Activity ◽  
Central Nucleus ◽  
Motor Nucleus ◽  
Dorsal Vagal Complex ◽  
Motility Index ◽  
Medial Nucleus ◽  
Dorsal Motor Nucleus ◽  
Stimulation Of

The aim of the study was to determine the effects of electrical stimulation of different locations in the central nucleus of amygdala (CNA) on gastric motility and spike activity in dorsal vagal complex. Gastric motility index (GMI) and firing rate (FR) of dorsal vagal complex neurons were measured in adult Wistar rats respectively. Neuronal spikes in dorsal vagal complex (DVC) were recorded extracellularly with single-barrel glass microelectrodes. Each type of responses elicited by electrical stimulation in medial (CEM) and lateral (CEL) subdivisions of CNA were recorded, respectively. GMI was significantly increased after stimulation of CEM (p<0.01), and significantly decreased in response to CEL stimulation (p<0.01). After stimulation of CEM, FR in medial nucleus of the solitary tract (mNST) decreased by 31.6 % (p<0.01) and that in dorsal motor nucleus of the vagus (DMNV) increased by 27.1 % (p<0.01). On the contrary, FR in mNST increased (p<0.01) and that in DMNV decreased in response to CEL stimulation (p<0.05). In conclusions, our findings indicated that different loci of CNA may mediate differential effects on gastric activity via changes in the firing of brainstem neurons controlling gut activity.

scholarly journals NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Xinyan Gao ◽  
Yongfa Qiao ◽  
Baohui Jia ◽  
Xianghong Jing ◽  
Bin Cheng ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gastric Motility ◽  
Low Frequency ◽  
Synaptic Activity ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Vagal Reflex ◽  
Precise Molecular Mechanism ◽  
Lines Of Evidence

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynapticμ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

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