AT1 receptors in the nucleus tractus solitarii mediate the interaction between the baroreflex and the cardiac sympathetic afferent reflex in anesthetized rats

2007 ◽  
Vol 292 (3) ◽  
pp. R1137-R1145 ◽  
Author(s):  
Wei-Zhong Wang ◽  
Lie Gao ◽  
Yan-Xia Pan ◽  
Irving H. Zucker ◽  
Wei Wang
Keyword(s):  
Extracellular Recording ◽  
Nucleus Tractus Solitarii ◽  
Ang Ii ◽  
Baroreflex Control ◽  
Anesthetized Rats ◽  
Before And After ◽  
Cardiac Sympathetic Afferent Reflex ◽  
Induced Changes

The cardiac “sympathetic afferent” reflex (CSAR) has been reported to increase sympathetic outflow and depress baroreflex function via a central angiotensin II (ANG II) mechanism. In the present study, we examined the role of ANG II type 1 (AT1) receptors in the nucleus tractus solitarii (NTS) in mediating the interaction between the CSAR and the baroreflex in anesthetized rats. We examined the effects of bilateral microinjection of AT1 receptor antagonist losartan (100 pmol) into the NTS on baroreflex control of renal sympathetic nerve activity (RSNA) before and after CSAR activation by epicardial application of capsaicin (0.4 μg). Using single-unit extracellular recording, we further examined the effects of CSAR activation on the barosensitivity of barosensitive NTS neurons and the effects of intravenous losartan (2 mg/kg) on CSAR-induced changes in activity of NTS barosensitive neurons. Bilateral NTS microinjection of losartan significantly attenuated the increases in arterial pressure, heart rate, and RSNA evoked by capsaicin but also markedly ( P < 0.01) reversed the CSAR-induced blunted baroreflex control of RSNA (Gainmax from 1.65 ± 0.10 to 2.22 ± 0.11%/mmHg). In 17 of 24 (70.8%) NTS barosensitive neurons, CSAR activation significantly ( P < 0.01) inhibited the baseline neuronal activity and attenuated the neuronal barosensitivity. In 11 NTS barosensitive neurons, intravenous losartan effectively ( P < 0.01) normalized the decreased neuronal barosensitivity induced by CSAR activation. In conclusion, blockade of NTS AT1 receptors improved the blunted baroreflex during CSAR activation, suggesting that the NTS plays an important role in processing the interaction between the baroreflex and the CSAR via an AT1 receptor-dependent mechanism.

Endogenous ANG II supports lumbar sympathetic activity in conscious sodium-deprived rats: role of area postrema

1998 ◽  
Vol 275 (1) ◽  
pp. R46-R55 ◽  
Author(s):  
Ling Xu ◽  
John P. Collister ◽  
John W. Osborn ◽  
Virginia L. Brooks
Keyword(s):  
Sympathetic Activity ◽  
Food Restriction ◽  
Sympathetic Nerve Activity ◽  
Area Postrema ◽  
Ang Ii ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Maximal Gain

This study tests the hypothesis that the area postrema (AP) is necessary for endogenous ANG II to chronically maintain lumbar sympathetic nerve activity (LSNA) and heart rate (HR) in conscious sodium-deprived rats. The effect of the ANG II type 1-receptor antagonist, losartan, on LSNA and HR was determined in rats that were either AP lesioned (APX) or sham lesioned. The sham rats were divided into groups, with (SFR) or without (SAL) food restriction, to control for the decreased food intake of APX rats. Before losartan, basal mean arterial pressure (MAP), HR, and baroreflex control of LSNA and HR were similar between groups, with the exception of lower maximal reflex LSNA and higher maximal gain of the HR-MAP curve in APX rats. In all groups, losartan similarly shifted ( P < 0.01) the LSNA-MAP curve to the left without altering maximal gain. Losartan also decreased ( P < 0.05) minimal LSNA in all groups, and suppressed ( P < 0.01) maximal LSNA (% of control) in SFR (240 ± 13 to 205 ± 15) and SAL (231 ± 21 to 197 ± 26) but not APX (193 ± 10 to 185 ± 8) rats. In general, losartan similarly shifted the HR-MAP curve to a lower MAP in all groups. The results suggest that the AP is not necessary for endogenous ANG II to chronically support LSNA and HR at basal and elevated MAP levels in sodium-deprived rats. However, the AP is required for endogenous ANG II to increase maximal reflex LSNA at low MAP levels.

Role of pp60c-src andp44/42 MAPK in ANG II-induced contraction of rat tonic gastrointestinal smooth muscles

2002 ◽  
Vol 283 (2) ◽  
pp. G390-G399 ◽  
Author(s):  
Rajinder N. Puri ◽  
Ya-Ping Fan ◽  
Satish Rattan
Keyword(s):  
Smooth Muscles ◽  
Specific Inhibitor ◽  
Effector Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Herbimycin A ◽  
Before And After ◽  
Mitogen Activated Protein ◽  
Induced Changes

We examined the role of mitogen-activated protein kinase ( p44/42 MAPK) in ANG II-induced contraction of lower esophageal sphincter (LES) and internal anal sphincter (IAS) smooth muscles. Studies were performed in the isolated smooth muscles and cells (SMC). ANG II-induced changes in the levels of phosphorylation of different signal transduction and effector proteins were determined before and after selective inhibitors. ANG II-induced contraction of the rat LES and IAS SMC was inhibited by genistein, PD-98059 [a specific inhibitor of MAPK kinases (MEK 1/2)], herbimycin A (a pp60c-src inhibitor), and antibodies to pp60c-src and p120ras GTPase-activating protein ( p120rasGAP). ANG II-induced contraction of the tonic smooth muscles was accompanied by an increase in tyrosine phosphorylation of p120 rasGAP. These were attenuated by genistein but not by PD-98059. ANG II-induced increase in phosphorylations of p44/42 MAPKs and caldesmon was attenuated by both genistein and PD-98059. We conclude that pp60c-src and p44/42 MAPKs play an important role in ANG II-induced contraction of LES and IAS smooth muscles.

scholarly journals Nitric oxide and angiotensin II regulate cardiovascular homeostasis and the arterial baroreflex control of heart rate in conscious lambs

2011 ◽  
Vol 13 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Stephanie J Wehlage ◽  
Francine G Smith
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Angiotensin Ii ◽  
Ang Ii ◽  
Arterial Baroreflex ◽  
Baroreflex Control ◽  
Before And After ◽  
Cardiovascular Homeostasis ◽  
New Evidence

To investigate the potential role of angiotensin II (Ang II) type 1 receptors (AT1Rs) as well as endogenously produced nitric oxide (NO) in regulating cardiovascular homeostasis during ontogeny, experiments were carried out in conscious lambs aged approximately 1 week ( N = 9) and 6 weeks ( N = 11). The arterial baroreflex control of heart rate (HR) was assessed before and after intravenous (IV) infusion of the selective AT1R antagonist, ZD 7155, before and after IV administration of the L-arginine analogue, NG-nitro-L-arginine methyl ester (L-NAME). In both groups, after ZD 7155 alone, mean arterial pressure decreased then increased after L-NAME. At 1 but not 6 weeks, HR decreased after ZD 7155 as well as after L-NAME. At 1 but not 6 weeks, there was a decrease in the HR range after ZD 7155 and after ZD 7155 + L-NAME, as compared to control. There was also a decrease in minimum HR after ZD 7155 + L-NAME at 1 week. These data provide new evidence that, together, Ang II and NO regulate cardiovascular homeostasis as well as the arterial baroreflex of HR early in life which may help to explain the activation of these two systems early in life.

scholarly journals The Effect of Dual Language Activation on L2-Induced Changes in L1 Speech within a Code-Switched Paradigm

Languages ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 114
Author(s):  
Ulrich Reubold ◽  
Sanne Ditewig ◽  
Robert Mayr ◽  
Ineke Mennen
Keyword(s):  
Dual Language ◽  
Native Speakers ◽  
Predictor Variable ◽  
Predictor Variables ◽  
Acoustic Measures ◽  
Before And After ◽  
Language Activation ◽  
Dual Activation ◽  
Induced Changes

The present study sought to examine the effect of dual language activation on L1 speech in late English–Austrian German sequential bilinguals, and to identify relevant predictor variables. To this end, we compared the English speech patterns of adult migrants to Austria in a code-switched and monolingual condition alongside those of monolingual native speakers in England in a monolingual condition. In the code-switched materials, German words containing target segments known to trigger cross-linguistic interaction in the two languages (i.e., [v–w], [ʃt(ʁ)-st(ɹ)] and [l-ɫ]) were inserted into an English frame; monolingual materials comprised English words with the same segments. To examine whether the position of the German item affects L1 speech, the segments occurred either before the switch (“He wants a Wienerschnitzel”) or after (“I like Würstel with mustard”). Critical acoustic measures of these segments revealed no differences between the groups in the monolingual condition, but significant L2-induced shifts in the bilinguals’ L1 speech production in the code-switched condition for some sounds. These were found to occur both before and after a code-switch, and exhibited a fair amount of individual variation. Only the amount of L2 use was found to be a significant predictor variable for shift size in code-switched compared with monolingual utterances, and only for [w]. These results have important implications for the role of dual activation in the speech of late sequential bilinguals.

Reactive Oxygen Species-Mediated Homologous Downregulation of Angiotensin II Type 1 Receptor Mrna by Angiotensin II

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 688-688
Author(s):  
Toshihiro Ichiki ◽  
Kotaro Takeda ◽  
Akira Takeshita
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Crucial Role ◽  
Oxygen Species ◽  
Ang Ii ◽  
Stimulation Of

58 Recent studies suggest a crucial role of reactive oxygen species (ROS) for the signaling of Angiotensin II (Ang II) through type 1 Ang II receptor (AT1-R). However, the role of ROS in the regulation of AT1-R expression has not been explored. In this study, we examined the effect of an antioxidant on the homologous downregulation of AT1-R by Ang II. Ang II (10 -6 mol/L) decreased AT1-R mRNA with a peak suppression at 6 hours of stimulation in rat aortic vascular smooth muscle cells (VSMC). Ang II dose-dependently (10 -8 -10 -6 ) suppressed AT1-R mRNA at 6 hours of stimulation. Preincubation of VSMC with N-acetylcysteine (NAC), a potent antioxidant, almost completely inhibited the Ang II-induced downregulation of AT1-R mRNA. The effect of NAC was due to stabilization of the AT1-R mRNA that was destabilized by Ang II. Ang II did not affect the promoter activity of AT1-R gene. Diphenylene iodonium (DPI), an inhibitor of NADH/NADPH oxidase failed to inhibit the Ang II-induced AT1-R mRNA downregulation. The Ang II-induced AT1-R mRNA downregulation was also blocked by PD98059, an extracellular signal-regulated protein kinase (ERK) kinase inhibitor. Ang II-induced ERK activation was inhibited by NAC as well as PD98059 whereas DPI did not inhibit it. To confirm the role of ROS in the regulation of AT1-R mRNA expression, VSMC were stimulated with H 2 O 2 . H 2 O 2 suppressed the AT1-R mRNA expression and activated ERK. These results suggest that production of ROS and activation of ERK are critical for downregulation of AT1-R mRNA. The differential effect of NAC and DPI on the downregulation of AT1-R mRNA may suggest the presence of other sources than NADH/NADPH oxidase pathway for ROS in Ang II signaling. Generation of ROS through stimulation of AT1-R not only mediates signaling of Ang II but may play a crucial role in the adaptation process of AT1-R to the sustained stimulation of Ang II.

Abstract P059: A A Role of Aminopeptidase A in the Brain on Cardiovascular Regulation of Conscious Rat

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Akio Ishida ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Drinking Behavior ◽  
Cardiovascular Regulation ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Aminopeptidase A ◽  
The Brain

Objective: Aminopeptidase A (APA) have important role in conversion of Ang II to Ang III. Intravenous APA administration lowers blood pressure in hypertensive rats. In contrast, APA inhibition in the brain lowers blood pressure in hypertensive rats. Therefore APA might have different role on cardiovascular regulation. However, a role of APA and Ang III on cardiovascular regulation especially in the brain has not been fully understood. Our purpose of present study was to investigate a role of APA and Ang III in the brain on cardiovascular regulation in conscious state. Method: 12-13 weeks old Wistar Kyoto rat (WKY) and 12-16 weeks old spontaneously hypertensive rat (SHR) were used. i) APA distribution in the brain was evaluated by immunohistochemistry. Protein expression of APA was evaluated by Western blotting. Enzymatic activity of APA was evaluated using L-glutamic acid γ-(4-nitroanilide) as a substrate. ii) WKY received icv administration of Ang II 25ng/2μL and Ang III 25ng/2μL. We recorded change in mean arterial pressure (MAP) in conscious and unrestraied state and measured induced drinking time. iii) SHR received icv administeration of recombinant APA 400ng/4μL. We recorded change in MAP in conscious and unrestraied state and measured induced drinking time. Result: i) APA was diffusely immunostained in the cells of brain stem including cardiovascular regulatory area such as rostral ventrolateral medulla. Protein expression and APA activity in the brain were similar between WKY (n=3) and SHR (n=3).ii) Icv administration of Ang II increased MAP by 33.8±3.8 mmHg and induced drinking behavior for 405±90 seconds (n=4). Icv administration of Ang III also increased MAP by 24.7±2.4 mmHg and induced drinking behavior for 258±62 seconds (n=3). These vasopressor activity and induced drinking behavior was completely blocked by pretretment of angiotensin receptor type 1 blocker.iii) Icv administration of APA increased MAP by 10.0±1.7 mmHg (n=3). Conclusion: These results suggested that Ang III in the brain increase blood pressure by Angiotensin type 1 receptor dependent mechanism and APA in the brain may involved in blood pressure regulation as a vasopressor enzyme.

scholarly journals Role of nitric oxide-containing factors in the ventilatory and cardiovascular responses elicited by hypoxic challenge in isoflurane-anesthetized rats

2014 ◽  
Vol 116 (11) ◽  
pp. 1371-1381 ◽  
Author(s):  
James P. Mendoza ◽  
Rachael J. Passafaro ◽  
Santhosh M. Baby ◽  
Alex P. Young ◽  
James N. Bates ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Cardiovascular Responses ◽  
Vital Role ◽  
Initial Increase ◽  
Ventilatory Responses ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Before And After

Exposure to hypoxia elicits changes in mean arterial blood pressure (MAP), heart rate, and frequency of breathing (fr). The objective of this study was to determine the role of nitric oxide (NO) in the cardiovascular and ventilatory responses elicited by brief exposures to hypoxia in isoflurane-anesthetized rats. The rats were instrumented to record MAP, heart rate, and fr and then exposed to 90 s episodes of hypoxia (10% O2, 90% N2) before and after injection of vehicle, the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME), or the inactive enantiomer d-NAME (both at 50 μmol/kg iv). Each episode of hypoxia elicited a decrease in MAP, bidirectional changes in heart rate (initial increase and then a decrease), and an increase in fr. These responses were similar before and after injection of vehicle or d-NAME. In contrast, the hypoxia-induced decreases in MAP were attenuated after administration of l-NAME. The initial increases in heart rate during hypoxia were amplified whereas the subsequent decreases in heart rate were attenuated in l-NAME-treated rats. Finally, the hypoxia-induced increases in fr were virtually identical before and after administration of l-NAME. These findings suggest that NO factors play a vital role in the expression of the cardiovascular but not the ventilatory responses elicited by brief episodes of hypoxia in isoflurane-anesthetized rats. Based on existing evidence that NO factors play a vital role in carotid body and central responses to hypoxia in conscious rats, our findings raise the novel possibility that isoflurane blunts this NO-dependent signaling.

Angiotensin II modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism in rabbits

1995 ◽  
Vol 269 (5) ◽  
pp. R1009-R1016 ◽  
Author(s):  
Y. Nishida ◽  
K. L. Ryan ◽  
V. S. Bishop
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Ang Ii ◽  
Arterial Baroreflex ◽  
Baroreflex Control ◽  
Renal Sympathetic Nerve Activity ◽  
Baroreflex Function ◽  
Before And After ◽  
Dose Dependent ◽  
Renal Sympathetic

To test the hypothesis that angiotensin II (ANG II) modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism, we examined the effects of intravertebral infusion of ANG II on baroreflex function curves before and after intravertebral administration of the alpha 1-adrenoreceptor antagonist prazosin. Rabbits were chronically instrumented with subclavian and vertebral arterial catheters, venous catheters, and aortic and vena caval occludes. Baroreflex curves were obtained by relating heart rate (HR) to mean arterial pressure during increases and decreases in arterial pressure. Intravertebral infusions of ANG II (5, 10, and 20 ng.kg-1.min-1) produced a dose-dependent shift of the midrange of the curve toward higher pressures (64 +/- 1 to 68 +/- 1, 76 +/- 1, and 85 +/- 2 mmHg, respectively). Pretreatment with prazosin (10 micrograms/kg) via the vertebral artery markedly reduced the shift in the baroreflex curve induced by the highest dose of ANG II (64 +/- 2 to 70 +/- 2 mmHg). These data suggest that ANG II resets the operating point of the HR baroreflex curve to a higher blood pressure and that this effect is mediated via a central alpha 1 mechanism. When the effects of vertebral ANG II on the baroreflex control of renal sympathetic nerve activity (RSNA) were examined, intravertebral administration of ANG II, while reducing the gain and the maximum RSNA, did not reset the RSNA baroreflex curve. These data suggest that ANG II acutely resets the HR baroreflex but not the RSNA baroreflex and that the resetting involves an alpha 1-adrenergic mechanism.

Role of periaqueductal gray in the pressor response produced by central injections of angiotensin II

1993 ◽  
Vol 265 (5) ◽  
pp. R1052-R1059
Author(s):  
L. R. Portis ◽  
S. J. Lewis ◽  
M. J. Brody
Keyword(s):  
Electrical Stimulation ◽  
Angiotensin Ii ◽  
Fluorescent Dyes ◽  
Pressor Response ◽  
Periaqueductal Gray ◽  
Ang Ii ◽  
Hemodynamic Responses ◽  
Anesthetized Rats ◽  
Stimulation Of

The present studies were undertaken to determine the role of rostral periaqueductal gray (PAG) in mediating the pressor effect produced by intracerebroventricular (icv) injection of angiotensin II (ANG II, 200 ng). Two functionally and anatomically distinct sites were identified in rostral PAG: a dorsomedial site involved in the hemodynamic responses produced by electrical stimulation of the anteroventral third ventricle (AV3V) region and a ventromedial site required for the pressor response elicited by icv administration of ANG II. In Saffan-anesthetized rats, injection of lidocaine (LIDO, 4%) in dorsomedial PAG, but not in ventromedial PAG, significantly attenuated the decrease in hindquarter resistance (HQR) produced by electrical stimulation of the AV3V region, and the poststimulatory increase in mean arterial pressure (MAP) and HQR. The injection of LIDO in ventromedial PAG had no effect on the hemodynamic responses produced by electrical stimulation of the AV3V region in anesthetized rats but significantly attenuated the pressor response produced by icv administration of ANG II in conscious rats. The hypothesis that these two sites receive separate projections was addressed by microinjecting two retrogradely transported fluorescent dyes, Fluoro-Gold and Fast Blue. The anatomic findings suggest that separation of the pathways activated by electrical and chemical stimulation of the AV3V region occurs at the level of rostral PAG.

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.

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