Abstract 441: Sex Differences in Microglia Activation During Subpressor Dose of Angiotensin (Ang) II Sensitization of Subsequent Pressor Dose of Ang II

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Meredith Hay ◽  
Farmin Samareh- Jahani ◽  
Baojian Xue ◽  
Alan K Johnson
Keyword(s):  
Sex Differences ◽  
Experimental Design ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Brain Slices ◽  
Microglia Activation ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Activated Microglia ◽  
The Brain

In previous studies using the Induction-Delay-Expression (I-D-E) experimental design we have shown that there are sex differences in the effects of one-week Ang II pre-treatment to sensitize the brain to produce an enhanced hypertensive response to subsequent Ang II. In other studies, we have shown that females are protected from hypertension and brain infiltration of T lymphocytes during Ang II infusion. The purpose of the present study was to test whether there is a sex difference in brain microglia activation on the sensitizing effects of Ang II. The present studies followed an I-D-E experimental design. Three male and three female Sprague-Dawley rats were assigned to each of the following experimental groups: 1) Control ( I saline + D) ; 2) I-Ang II+D ( I with subpressor dose of Ang II, 10 ng/kg/min); 3) I-saline+D+E-Ang II (I with saline plus E with a pressor dose of Ang II, 120 ng/kg/min); 4) I-Ang II+D+E-Ang II (I with subpressor dose of Ang II plus E with pressor dose of Ang II). At the end of the experiment, animals were anesthetized and perfused with formalin. Thirty-micron frozen slices of the area postrema (AP), nucleus tractus solitarius (NTS), and subfornical organ (SFO) were processed for IHC staining with IBa-1 microglia antibody (WAKO, 1:200). The number of IBa-1+ activated microglia (MG) in each region were counted in an approx 3 consecutive brain slices from 3 separate animals. The subpressor dose of Ang II resulted in a significant increase in NTS activated microglia in males (MG 19.2 vs. 5.1) but not in females (MG 1.5 vs 2.3) when compared to control. In females, the pressor dose of Ang II did not increase the activated microglia in the NTS. The numbers of activated microglia in the AP was similar in males and females in the I-Ang II+D+E-Ang II group, but in the I-Sal+D+E-Ang II, males had greater number of MG in the AP as compared to females (21.5 vs 11.8, P=0.05). The number of MG in the SFO were low across all groups compared to the number of MG in other regions examined (males I-Ang II+D+E-Ang II group averaged 3.9 MG vs females averaged 2.3 MG). These results suggest that sex differences observed in the brain sensitization to Ang II may involve differential induction of microglia activation in selective brain regions important for Ang II generation of hypertension.

Cardiovascular actions of microinjections of angiotensin II in the brain stem of rats

1984 ◽  
Vol 246 (5) ◽  
pp. R811-R816 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Brain Stem ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Cardiovascular Response ◽  
Pressor Response ◽  
Ang Ii ◽  
The Brain

The blood pressure and heart rate responses to microinjection of angiotensin II (ANG II) into the brain stem of urethan-anesthetized rats were studied. Microinjection of ANG II into the area postrema (AP) resulted in significant elevation of blood pressure and significant reduction of heart rate. Microinjection into the region of the nucleus tractus solitarius (NTS) yielded a significant dose-dependent elevation in blood pressure and consistent increases in heart rate. The response to microinjection of ANG II into the region of the NTS was not due to leakage into the peripheral circulation, since intravenous administration of the ANG II antagonist, saralasin, did not attenuate the response. In fact, the cardiovascular response was increased after peripheral ANG II blockade, and the heart rate, which was consistently but not significantly elevated by NTS injection alone, was significantly elevated after saralasin pretreatment. Thermal ablation of the AP did not change the heart rate or the pressor response to microinjection of ANG II into the region of the NTS, indicating that the response was not mediated through the AP.

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.

Electrophysiological evidence that systemic angiotensin influences rat area postrema neurons

1990 ◽  
Vol 258 (1) ◽  
pp. R70-R76 ◽  
Author(s):  
S. Papas ◽  
P. Smith ◽  
A. V. Ferguson
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Cell Types ◽  
Male Rats ◽  
Ang Ii ◽  
Adrenergic Agonist ◽  
Arterial Blood ◽  
Spontaneous Activities ◽  
Single Unit Recordings ◽  
Body Fluid Balance

Extracellular single-unit recordings from neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS) in anesthetized male rats demonstrated that most cells in these regions have spontaneous activities of 5 Hz or less. Systemic angiotensin (ANG II) (50-500 ng) enhanced the activity of 55% of AP cells tested (n = 76), whereas 53% of tested NTS neurons (n = 62) were inhibited by ANG II. To determine whether these neurons were influenced specifically by circulating ANG II or by the accompanying increase in mean arterial blood pressure (BP), the effects of adrenergic agonists given intravenously on ANG II influenced neurons were also examined. Subsequently two cell types were characterized: cells responding to iv ANG II but not to the adrenergic agonist ("ANG II sensitive") and cells responding in a similar way to both agents ("BP sensitive"). Most ANG II-responsive neurons in the AP (53.5%) and the NTS (65%) were determined to be BP sensitive. These data demonstrate that ANG II influences the activity of AP neurons. In addition, there exists a second population of AP neurons apparently responsive to perturbations of the cardiovascular system. These studies further emphasize the potential roles of the AP in the regulation of body fluid balance.

Baroreceptor reflex modulation by circulating angiotensin II is mediated by AT1 receptors in the nucleus tractus solitarius

2007 ◽  
Vol 293 (6) ◽  
pp. R2267-R2278 ◽  
Author(s):  
Peter S. P. Tan ◽  
Suzanne Killinger ◽  
Jouji Horiuchi ◽  
Roger A. L. Dampney
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Critical Role ◽  
Baroreceptor Reflex ◽  
Reflex Modulation ◽  
Ang Ii ◽  
Baroreflex Control ◽  
Background Infusion ◽  
Continuous Background

Circulating ANG II modulates the baroreceptor reflex control of heart rate (HR), at least partly via activation of ANG II type 1 (AT1) receptors on neurons in the area postrema. In this study, we tested the hypothesis that the effects of circulating ANG II on the baroreflex also depend on AT1 receptors within the nucleus tractus solitarius (NTS). In confirmation of previous studies in other species, increases in arterial pressure induced by intravenous infusion of ANG II had little effect on HR in urethane-anesthetized rats, in contrast to the marked bradycardia evoked by equipressor infusion of phenylephrine. In the presence of a continuous background infusion of ANG II, the baroreflex control of HR was shifted to higher levels of HR but had little effect on the baroreflex control of renal sympathetic activity. The modulatory effects of circulating ANG II on the cardiac baroreflex were significantly reduced by microinjection of candesartan, an AT1 receptor antagonist, into the area postrema and virtually abolished by microinjections of candesartan into the medial NTS. After acute ablation of the area postrema, a background infusion of ANG II still caused an upward shift of the cardiac baroreflex curve, which was reversed by subsequent microinjection of candesartan into the medial NTS. The results indicate that AT1 receptors in the medial NTS play a critical role in modulation of the cardiac baroreflex by circulating ANG II via mechanisms that are at least partly independent of AT1 receptors in the area postrema.

Differential Effects of Angiotensin II and Angiotensin-(1-7) at the Nucleus Tractus Solitarii of Transgenic Rats with Low Brain Angiotensinogen

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 700-700
Author(s):  
Aurea S Couto ◽  
Ovidiu Baltatu ◽  
Robson A S Santos ◽  
Detlev Ganten ◽  
Michael Bader ◽  
...  
Keyword(s):  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Renin Angiotensin System ◽  
Nucleus Tractus Solitarii ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Baroreflex Control ◽  
Sd Rats ◽  
The Brain

P42 The potential importance of permanent alteration of the brain renin-angiotensin system on angiotensin (Ang) II and Ang-(1-7) effects at the level of the nucleus tractus solitarii (NTS) was investigated in transgenic rats with a deficit in brain angiotensinogen production TGR(ASrAOGEN) (TGR). Ang II (10 pmol), Ang-(1-7) (10 pmol) or NaCl (0.9%/ 50 nl) were microinjected into the NTS of urethane-anesthetized TGR (n=28) and Sprague-Dawley (SD, n=22) rats. Mean arterial pressure (MAP) and heart rate (HR) were measured via a femoral artery catheter and the baroreflex control of heart rate was evaluated after increases in MAP induced by phenylephrine (baroreflex bradycardia). Ang II microinjections into the NTS of the TGR induced a higher decrease in MAP and HR (-37 ± 5 mmHg and -69 ± 12.5 beats/min, respectively) in comparison with SD rats (-18 ± 1 mmHg and -51 ± 11 beats/min, respectively). In contrast, changes after Ang-(1-7) microinjections into the NTS of TGR (-6 ± 1 mmHg and -13 ± 5 beats/min) were significantly smaller than that induced in SD (-11 ± 2 mmHg and -24 ± 8 beats/min.). The baroreflex sensitivity was accentuated in TGR in comparison to SD rats (0.69 ± 0.06 vs. 0.44 ± 0.03 ms/ mmHg). Ang II microinjection into the NTS produced similar attenuation in the baroreflex bradycardia in both SD (0.28 ± 0.07 vs. 0.5 ± 0.07 ms/ mmHg, before injection) and TGR (0.44 ± 0.1 vs. 0.82 ± 0.1ms/ mmHg, before injection). Ang-(1-7) microinjection elicited a facilitation of the baroreflex bradycardia in SD (0.62 ± 0.1 vs. 0.4 ± 0.03 ms/ mmHg, before injection). However in TGR, baroreflex bradycardia after Ang-(1-7) was not different from saline microinjection. These results indicate that a permanent inhibition of angiotensinogen synthesis in the brain can lead to a functional up-regulation of Ang II receptors. However, the putative Ang-(1-7) receptors seem to be desensitized in the NTS of these transgenic rats. The alterated baroreflex sensitivity, both before and after Ang microinjection, indicates the functionally relevant decrease in brain Ang in TGR and supports differential regulatory mechanisms for the effects of the two Ang peptides.

Angiotensin II attenuates baroreflexes at nucleus tractus solitarius of rats

1986 ◽  
Vol 250 (2) ◽  
pp. R193-R198 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Baroreflex Sensitivity ◽  
Nucleus Tractus Solitarius ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Baroreceptor Reflexes ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
The Brain

Microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius (NTS) has been shown to produce a dose-dependent increase in blood pressure and heart rate. We have tested the effect of subpressor infusions of ANG II (10 ng . kg-1 . min-1) in the NTS on reflex bradycardia after intravenous administration of the vasoconstrictor phenylephrine (1-12 micrograms) in normotensive urethan-anesthetized rats. ANG II within the brain is thought to contribute to the decreased baroreflex sensitivity in spontaneously hypertensive rats (SHR). The sensitivity of the baroreflex was significantly decreased by the infusion of ANG II (1.01 +/- 0.08) compared with control (2.41 +/- 0.51) in the normotensive animals. Baroreflex sensitivity was significantly decreased in SHR (0.40 +/- 0.21) compared with normotensive animals. We conclude that ANG II within the NTS can inhibit the function of baroreceptor reflexes in normotensive animals, suggesting that the endogenous peptide may perform an inhibitory role in the baroreflex arc, and this is further evidence that central ANG II is involved in blood pressure of SHR.

Brain Angiotensinergic Regulation of the Immune System: Implications for Cardiovascular and Neuroendocrine Responses

2020 ◽  
Vol 20 (1) ◽  
pp. 15-24
Author(s):  
Michele Iovino ◽  
Tullio Messana ◽  
Giovanni De Pergola ◽  
Emanuela Iovino ◽  
Edoardo Guastamacchia ◽  
...  
Keyword(s):  
Immune System ◽  
Inflammatory Responses ◽  
Area Postrema ◽  
Chronic Hypertension ◽  
Ang Ii ◽  
High Concentration ◽  
Mesh Terms ◽  
Neuroendocrine Responses ◽  
The Brain ◽  
Cardiovascular Functions

Objective: The Renin-Angiotensin-Aldosterone System (RAAS) plays a major role in the regulation of cardiovascular functions, water and electrolytic balance, and hormonal responses. We perform a review of the literature, aiming at providing the current concepts regarding the angiotensin interaction with the immune system in the brain and the related implications for cardiovascular and neuroendocrine responses. Methods: Appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined. Results: Angiotensin II (ANG II), beside stimulating aldosterone, vasopressin and CRH-ACTH release, sodium and water retention, thirst, and sympathetic nerve activity, exerts its effects on the immune system via the Angiotensin Type 1 Receptor (AT 1R) that is located in the brain, pituitary, adrenal gland, and kidney. Several actions are triggered by the binding of circulating ANG II to AT 1R into the circumventricular organs that lack the Blood-Brain-Barrier (BBB). Furthermore, the BBB becomes permeable during chronic hypertension thereby ANG II may also access brain nuclei controlling cardiovascular functions. Subfornical organ, organum vasculosum lamina terminalis, area postrema, paraventricular nucleus, septal nuclei, amygdala, nucleus of the solitary tract and retroventral lateral medulla oblongata are the brain structures that mediate the actions of ANG II since they are provided with a high concentration of AT 1R. ANG II induces also T-lymphocyte activation and vascular infiltration of leukocytes and, moreover, oxidative stress stimulating inflammatory responses via inhibition of endothelial progenitor cells and stimulation of inflammatory and microglial cells facilitating the development of hypertension. Conclusion: Besides the well-known mechanisms by which RAAS activation can lead to the development of hypertension, the interactions between ANG II and the immune system at the brain level can play a significant role..

scholarly journals SAT-605 Characterization of Dual Projection Patterns of Refeeding-Activated Neurons in the Parasubthalamic Nucleus

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Gabor Wittmann ◽  
Nicholas Cosentino ◽  
Ronald M Lechan
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Brain Regions ◽  
Central Nucleus ◽  
Free Access ◽  
Target Area ◽  
Sprague Dawley ◽  
Bed Nucleus ◽  
Alexa Fluor ◽  
The Brain

Abstract We have observed that following a fast, animals terminate their food intake within 2h after refeeding accompanied by a pattern of neuronal activation as identified by c-fos immunostaining that involves a number of brain regions associated with the regulation of food intake including the nucleus tractus solitarius (NTS), parabrachial nucleus (PBN), central nucleus of the amygdala (CEA), hypothalamic arcuate and paraventricular nuclei, and bed nucleus of the stria terminalis. We also observed striking c-fos activation in the posterior-lateral hypothalamus called the parasubthalamic nucleus or PSTN, raising the possibility that it may also be an important anorectic center in the brain. To establish how the PSTN is integrated into the CNS, we performed dual-label retrograde tract tracing studies to characterize whether refeeding-activated PSTN neurons project to one, or more than one target area in the CNS. Adult, Sprague-Dawley rats received dual stereotaxic injections of Alexa Fluor 488- and Alexa Fluor 555-conjugated cholera toxin β subunit (CTB; 0.1%, 0.5–1 µl volume) into the 1) PBN and NTS, 2) PBN and CEA and 3) NTS and CEA. After 7–12 days, the animals were fasted for 24 h and then given free access to food for 2 h before euthanasia by transcardial perfusion with 4% paraformaldehyde. Brains with successful dual injections were further processed for c-fos immunohistochemistry. The results showed that 26.5±3.8% of PSTN neurons projecting to the PBN also project to the CEA, and 34.6±7.6% of PSTN neurons that project to the CEA also project to the PBN. In addition, 20.2±2.7% of PSTN neurons that project to the PBN also project to the NTS, and 38.1±9.7% of PSTN neurons that project to the NTS also project to the PBN. Furthermore, 35.0±12.5% of PSTN neurons that project to the CEA project to the NTS and 37.1±4.0% of PSTN neurons that project to the NTS project to the CEA. Finally, up to 15% of the neurons with dual projections to the PBN and CEA contained c-fos after refeeding; up to 18% of the neurons with dual projections to the PBN and NTS contained c-fos; and up to 30% of neurons with dual projections to the NTS and CEA contained c-fos. We conclude that a large number of PSTN neurons have more than one projection site within the brain, thus the PSTN appears to have the capability of simultaneously communicating information about appetite to several, major feeding-related sites within the brain, presumably to terminate feeding.

Neuropeptide action in nucleus tractus solitarius: angiotensin specificity and hypertensive rats

1985 ◽  
Vol 249 (3) ◽  
pp. R341-R347 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Heart Rate ◽  
Nucleus Tractus Solitarius ◽  
Dose Range ◽  
Cardiovascular Effects ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto

We have reported that microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius of urethan-anesthetized normotensive rats produces an increase in mean arterial pressure (MAP) over the dose range 50-500 pmol. The effect in spontaneously hypertensive rats (SHR) is now reported. Over the range 100-500 pmol SHR exhibit increases in MAP and heart rate greater than Wistar-Kyoto or Sprague-Dawley rats. SHR did not exhibit exaggerated responses to intravenous phenylephrine, suggesting a central site of increased responsiveness to ANG II. We also found depressor effects in Sprague-Dawley at lower doses (0.1 and 1 pmol). The decreases in MAP were extremely variable and not dose related. A selected dose of additional neuropeptides identified in the NTS was tested. Somatostatin, bradykinin, and vasoactive intestinal peptide (0.5 nmol) were without cardiovascular effects. Oxytocin and vasopressin, however, produced significant increases in MAP. Substance P produced a very small but significant increase in heart rate and MAP. Interaction between the vasopressin and ANG II pressor effects was studied, and each proved to be independent.

Medullary CO2 chemoreceptor neuron identification by c-fos immunocytochemistry

1992 ◽  
Vol 73 (1) ◽  
pp. 96-100 ◽  
Author(s):  
M. Sato ◽  
J. W. Severinghaus ◽  
A. I. Basbaum
Keyword(s):  
Brain Stem ◽  
Nucleus Tractus Solitarius ◽  
Frozen Sections ◽  
Sprague Dawley ◽  
High Co2 ◽  
Fos Protein ◽  
Sprague Dawley Rats ◽  
Ventral Medullary Surface ◽  
Increased Activity ◽  
The Brain

In a search for CO2 chemoreceptor neurons in the brain stem, we used immunocytochemistry to monitor the expression of neuronal c-fos, a marker of increased activity, after 1 h of exposure to CO2 in five groups of Sprague-Dawley rats (294 +/- 20 g): five air breathing controls, three breathing 10% CO2, three breathing 13% CO2, three breathing 15% CO2, and three breathing 15% CO2 and treated with morphine (10 mg/kg sc). After exposure the rats were anesthetized with pentobarbital sodium and perfused intracardially with 4% paraformaldehyde. The brain stem was removed and cryoprotected, and then 50-microns frozen sections were cut and immunostained for the fos protein. Brain stem fos-immunoreactive neurons were plotted and counted in the superficial 0.5 mm of the ventral medullary surface. Thirteen to 15% CO2 evoked fos-like immunoreactivity (FLI) in 321 +/- 146 neurons/rat. Significant CO2-induced labeling was confined within the superficial 150 microns: 67% of identified cells were less than 50 microns below the surface, greater than 90% between 1.0 and 3.0 mm from the midline, and approximately 60% in the rostral half of the medulla. Thirteen to 15% CO2 also evoked FLI in the area of the nucleus tractus solitarius but not in other medullary regions. Morphine (10 mg/kg sc) did not suppress high CO2-evoked FLI in either the ventral medullary surface or the nucleus tractus solitarius, although it eliminated excitement and hyperventilation. We suggest that respiratory CO2 chemoreceptor neurons can be identified in rats by their expression of c-fos after 1 h of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

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