Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus

2005 ◽  
Vol 288 (4) ◽  
pp. R1014-R1020 ◽  
Author(s):  
Mostafa A. El-Haddad ◽  
Yaser Ismail ◽  
Dave Gayle ◽  
Michael G. Ross
Keyword(s):  
At1 Receptor ◽  
Receptor Blocker ◽  
At2 Receptor ◽  
Ang Ii ◽  
At1 Receptors ◽  
Pressor Responses ◽  
Ovine Fetus ◽  
Near Term ◽  
At2 Receptors

Swallowed volumes in the fetus are greater than adult values (per body weight) and serve to regulate amniotic fluid volume. Central ANG II stimulates swallowing, and nonspecific ANG II receptor antagonists inhibit both spontaneous and ANG II-stimulated swallowing. In the adult rat, AT1 receptors mediate both stimulated drinking and pressor activities, while the role of AT2 receptors is controversial. As fetal brain contains increased ANG II receptors compared with the adult brain, we sought to investigate the role of both AT1 and AT2 receptors in mediating fetal swallowing and pressor activities. Five pregnant ewes with singleton fetuses (130 ± 1 days) were prepared with fetal vascular and lateral ventricle (LV) catheters and electrocorticogram and esophageal electromyogram electrodes and received three studies over 5 days. On day 1 (ANG II), following a 2-h basal period, 1 ml artificial cerebrospinal fluid (aCSF) was injected in the LV. At time 4 h, ANG II (6.4 μg) was injected in the LV, and the fetus was monitored for a final 2 h. On day 3, AT1 receptor blocker (losartan 0.5 mg) was administered at 2 h, and ANG II plus losartan was administered at 4 h. On day 5, AT2 receptor blocker (PD-123319; 0.8mg) was administered at 2 h and ANG II plus PD-123319 at 4 h. In the ANG II study, LV injection of ANG II significantly increased fetal swallowing (0.9 ± 0.1 to 1.4 ± 0.1 swallows/min; P < 0.05). In the losartan study, basal fetal swallowing significantly decreased in response to blockade of AT1 receptors (0.9 ± 0.1 to 0.4 ± 0.1 swallows/min; P < 0.05), while central injection of ANG II in the presence of AT1 receptor antagonism did not increase fetal swallowing (0.6 ± 0.1 swallows/min). In the PD-123319 study, basal fetal swallowing did not change in response to blockade of AT2 receptor (0.9 ± 0.1 swallows/min), while central injection of ANG II in the presence of AT2 blockade significantly increased fetal swallowing (1.5 ± 0.1 swallows/min; P < 0.05). ANG II caused significant pressor responses in the control and PD-123319 studies but no pressor response in the presence of AT1 blockade. These data demonstrate that in the near-term ovine fetus, AT1 receptor but not AT2 receptors accessible via CSF contribute to dipsogenic and pressor responses.

scholarly journals The Receptor AT1 Appears to Be Important for the Maintenance of Bone Mass and AT2 Receptor Function in Periodontal Bone Loss Appears to Be Regulated by AT1 Receptor

2021 ◽  
Vol 22 (23) ◽  
pp. 12849
Author(s):  
Maria Laura de Souza Lima ◽  
Agnes Andrade Martins ◽  
Caroline Addison Carvalho Xavier de Medeiros ◽  
Gerlane Coelho Bernardo Guerra ◽  
Robson Santos ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Alveolar Bone ◽  
Experimental Studies ◽  
At1 Receptor ◽  
At2 Receptor ◽  
Ang Ii ◽  
Key Events

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.

scholarly journals Angiotensin II AT1 and AT2 Receptors Contribute to Maintain Basal Adrenomedullary Norepinephrine Synthesis and Tyrosine Hydroxylase Transcription

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2092-2101 ◽  
Author(s):  
Miroslava Jezova ◽  
Ines Armando ◽  
Claudia Bregonzio ◽  
Zu-Xi Yu ◽  
Sujuan Qian ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Receptor Binding ◽  
At1 Receptor ◽  
Receptor Protein ◽  
At2 Receptor ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Th Mrna ◽  
At2 Receptors

Angiotensin II (Ang II) AT1 receptors have been proposed to mediate the Ang II-dependent and the stress-stimulated adrenomedullary catecholamine synthesis and release. However, in this tissue, most of the Ang II receptors are of the AT2 type. We asked the question whether AT1 and AT2 receptors regulate basal catecholamine synthesis. Long-term AT1 receptor blockade decreased adrenomedullary AT1 receptor binding, AT2 receptor binding and AT2 receptor protein, rat tyrosine hydroxylase (TH) mRNA, norepinephrine (NE) content, Fos-related antigen 2 (Fra-2) protein, phosphorylated cAMP response element binding protein (pCREB), and ERK2. Long-term AT2 receptor blockade decreased AT2 receptor binding, TH mRNA, NE content and Fra-2 protein, although not affecting AT1 receptor binding or receptor protein, pCREB or ERK2. Angiotensin II colocalized with AT1 and AT2 receptors in ganglion cell bodies. AT2 receptors were clearly localized to many, but not all, chromaffin cells. Our data support the hypothesis of an AT1/AT2 receptor cross-talk in the adrenomedullary ganglion cells, and a role for both receptor types on the selective regulation of basal NE, but not epinephrine formation, and in the regulation of basal TH transcription. Whereas AT1 and AT2 receptors involve the Fos-related antigen Fra-2, AT1 receptor transcriptional effects include pCREB and ERK2, indicating common as well as different regulatory mechanisms for each receptor type.

Central neuronal activation and pressor responses induced by circulating ANG II: role of the brain aldosterone-“ouabain” pathway

2010 ◽  
Vol 299 (2) ◽  
pp. H422-H430 ◽  
Author(s):  
Bing S. Huang ◽  
Sara Ahmadi ◽  
Monir Ahmad ◽  
Roselyn A. White ◽  
Frans H. H. Leenen
Keyword(s):  
Mineralocorticoid Receptor ◽  
Pressor Response ◽  
Plasma Aldosterone ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Neuronal Activation ◽  
Intracerebroventricular Infusion ◽  
Pressor Responses ◽  
Hypothalamic Nuclei

An increase in plasma ANG II causes neuronal activation in hypothalamic nuclei and a slow pressor response, presumably by increasing sympathetic drive. We evaluated whether the activation of a neuromodulatory pathway, involving aldosterone and “ouabain,” is involved in these responses. In Wistar rats, the subcutaneous infusion of ANG II at 150 and 500 ng·kg−1·min−1 gradually increased blood pressure up to 60 mmHg at the highest dose. ANG II at 500 ng·kg−1·min−1 increased plasma ANG II by 4-fold, plasma aldosterone by 25-fold, and hypothalamic aldosterone by 3-fold. The intracerebroventricular infusion of an aldosterone synthase (AS) inhibitor prevented the ANG II-induced increase in hypothalamic aldosterone without affecting the increase in plasma aldosterone. Neuronal activity, as assessed by Fra-like immunoreactivity, increased transiently in the subfornical organ (SFO) but progressively in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). The central infusion of the AS inhibitor or a mineralocorticoid receptor blocker markedly attenuated the ANG II-induced neuronal activation in the PVN but not in the SON. Pressor responses to ANG II at 150 ng·kg−1·min−1 were abolished by an intracerebroventricular infusion of the AS inhibitor. Pressor responses to ANG II at 500 ng·kg−1·min−1 were attenuated by the central infusion of the AS inhibitor or the mineralocorticoid receptor blocker by 70–80% and by Digibind (to bind “ouabain”) by 50%. These results suggest a novel central nervous system mechanism for the ANG II-induced slow pressor response, i.e., circulating ANG II activates the SFO, leading to the direct activation of the PVN and SON, and, in addition, via aldosterone-dependent amplifying mechanisms, causes sustained activation of the PVN and thereby hypertension.

Abstract P152: Aminopeptidase A in the Brain Exerts Cardiovascular Action via Degradation of Kallidin to Bradykinin

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Cardiovascular Regulation ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Aminopeptidase A ◽  
Hoe 140 ◽  
Wistar Kyoto ◽  
The Brain

Objective: Aminopeptidase A (APA) degrades of various sympathomodulatory peptides such as angiotensin (Ang) II, cholecystkinin-8, neurokinin B and kallidin. APA activity is increased in the brain of hypertensive rats. A centrally acting APA inhibitor prodrug is currently under investigation in clinical trial for treatment of hypertension. In previous reports, a role of APA in the brain on cardiovascular regulation was researched focus on only renin-angiotensin system. We previously reported that intracerebroventricular(icv) administration of APA increased blood pressure and that this pressor response was partially blocked by angiotensin receptor blocker. In this study, we evaluated a role of APA on cardiovascular regulation focusing on peptides other than Ang II. Method: Eleven weeks old Wistar Kyoto rats were used. We icv administrated 800 ng/8 μL of APA after pretreatment of following drugs, i) 8μL of artificial cerebrospinal fluid (aCSF) as a control, ii) 80 nmol/8 μL of amastatin which is a non-specific aminopeptidase inhibitor, iii) 1 nmol/8 μL of HOE-140 which is a bradykinin receptor blocker to evaluate the involvement of degradation of kallidin to bradykinin by APA. Result: i) Icv administration of APA after pretreatment of aCSF increased blood pressure rapidly. Blood pressure reached a peak within 1 minute. The elevated blood pressure decreased gradually and reached baseline blood pressure in 10 minutes. A peak pressor response is 25.5±1.4 mmHg (n=5). ii) Icv pretreatment of amastatin or HOE-140 did not change the blood pressure. A peak pressor response induced by APA is 13.1±4.1 mmHg (n=6, p<0.05 vs aCSF). iii) Icv pretreatment of HOE-140 did not change the blood pressure. A peak pressor response induced by APA is 21.2±1.8 mmHg (n=4, p<0.05 vs aCSF). Conclusion: 1) Icv administration of APA increased blood pressure by APA enzymatic activity. 2) Cardiovascular regulation of APA in the brain is due to not only degradation of Ang II to Ang III but also degradation of kallidin to bradykinin. Clinical implication: We think inhibition of APA in the brain may be a unique therapeutic target which affects several cardiovascular peptides in the brain.

Abstract 421: The Subfornical Organ (SFO) Mediates CSF Na+ -induced Pressor Response via Activation of AT1 Receptors

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Missale A Tiruneh ◽  
Bing S Huang ◽  
Frans H Leenen
Keyword(s):  
Crucial Role ◽  
Major Part ◽  
Wistar Rats ◽  
Pressor Response ◽  
Electrolytic Lesion ◽  
Induced Responses ◽  
Ang Ii ◽  
At1 Receptors ◽  
Pressor Responses ◽  
The Brain

In salt-sensitive rats on high salt or rats with icv infusion of Na + , the increase in CSF [Na + ] leads to activation of the brain renin-angiotensin-aldosterone system and thereby to sympatho-excitation and hypertension. We tested whether the SFO and AT 1 receptors in the SFO play a crucial role in mediating the Na + -induced responses. In conscious Wistar rats, intra-SFO infusion of Na + -rich aCSF increased BP in a dose-related manner, whereas mannitol with the same osmolarity had no effects. Intra-SFO infusion of the AT 1 receptor blocker candesartan (cand.,10 μg) abolished pressor responses to intra-SFO infusion of Ang II (80 ng) or Na + -rich aCSF (0.45-0.6 M NaCl), and prevented 50% of the BP increase induced by icv infusion of Na + -rich aCSF (0.3 M NaCl, 4 μl/min for 6 min). In another set of Wistar rats, electrolytic lesion of the SFO prevented 50-65% of BP increases induced by icv infusion of Na + -rich aCSF or Ang II (5 ng/min). These data suggest that the SFO neurons are Na + -sensitive and via AT 1 receptors mediate a major part of the pressor response to CSF Na + . Data=means±SE (n=5-7). *p<.05 vs vehicle or sham lesion.

scholarly journals Evidence for a role of protein kinase C in hypoxic pulmonary vasoconstriction

1999 ◽  
Vol 276 (1) ◽  
pp. L90-L95 ◽  
Author(s):  
Norbert Weissmann ◽  
Robert Voswinckel ◽  
Thorsten Hardebusch ◽  
Simone Rosseau ◽  
Hossein Ardeschir Ghofrani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nadph Oxidase ◽  
Superoxide Anion ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Ang Ii ◽  
Pkc Inhibitor ◽  
Pulmonary Vasoconstriction ◽  
Pressor Responses ◽  
Hypoxic Vasoconstriction

Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion to ventilation, thus optimizing gas exchange. NADPH oxidase-related superoxide anion generation has been suggested as part of the signaling response to hypoxia. Because protein kinase (PK) C activation can occur during hypoxia and PKC activation is known to be critical for NADPH oxidase stimulation in different cell types, we probed the role of PKC in hypoxic vasoconstriction in intact rabbit lungs. Control vasoconstrictor responses were elicited by angiotensin II (ANG II) and the stable thromboxane analog U-46619. Portions of the experiments were performed while NO synthesis and prostanoid generation were blocked with N G-monomethyl-l-arginine and acetylsalicylic acid to avoid confounding effects due to interference with these vasoactive mediators. The PKC inhibitor H-7 (10–50 μM) caused dose-dependent inhibition of HPV, but this agent lacked specificity because ANG II- and U-46619-induced vasoconstrictions were correspondingly suppressed. In contrast, low concentrations of the specific PKC inhibitor bisindolylmaleimide I (BIM; 1–15 μM) strongly inhibited the hypoxic vasoconstriction without any interference with the responses to the pharmacological agents. Superimposable dose-inhibition curves were also obtained for BIM when lung NO synthesis and prostanoid generation were blocked throughout the experiments. Under either condition, BIM did not affect normoxic vascular tone. The PKC activator farnesylthiotriazole (FTT), ascertained to stimulate rabbit NADPH oxidase by provocation of alveolar macrophage superoxide anion generation in vitro, caused rapid-onset, transient pressor responses in normoxic lungs. After FTT, the hypoxic vasoconstrictor response was totally suppressed, in contrast to the largely maintained pressor responses to ANG II and U-46619. The lungs became refractory even to delayed hypoxic challenges after FTT application. In conclusion, these data support the concept that activation of PKC is involved in the transduction pathway forwarding pulmonary vasoconstriction in response to alveolar hypoxia.

Modulation of K+ and Ca2+ currents in cultured neurons by an angiotensin II type 1a receptor peptide

1997 ◽  
Vol 273 (3) ◽  
pp. C1040-C1048 ◽  
Author(s):  
M. Zhu ◽  
R. R. Neubig ◽  
S. M. Wade ◽  
P. Posner ◽  
C. H. Gelband ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
G Protein ◽  
At1 Receptor ◽  
Delayed Rectifier ◽  
Cultured Neurons ◽  
Ang Ii ◽  
Cytoplasmic Loop ◽  
At1 Receptors ◽  
The Third ◽  
Intracellular Changes

Angiotensin II (ANG II) inhibits delayed rectifier K+ current (IK) and stimulates total Ca2+ current (ICa) in neurons cocultured from newborn rat hypothalamus and brain stem, effects mediated via ANG II type 1 (AT1) receptors. Here, we identify potential G protein activator regions of the AT1 receptor responsible for initiating the intracellular changes that lead to alterations in these currents. Intracellular application into cultured neurons of a peptide corresponding to the third cytoplasmic loop of the AT1 receptor (AT1a/i3) mimicked the actions of ANG II on IK and ICa, whereas application of a peptide corresponding to the second cytoplasmic loop (AT1a/i2) did not alter these currents. This modulation of IK and ICa by AT1a/i3 involves intracellular messengers (G alpha q, protein kinase C, and intracellular Ca2+) that are identical to those involved in the modulation of IK and ICa following ANG II activation of AT1 receptors. These data provide functional evidence for a role of the third cytoplasmic loop of the AT1 receptor in G protein coupling and subsequent modulation of ion channel effectors.

scholarly journals Interaction between Angiotensin Type 1, Type 2, and Mas Receptors to Regulate Adult Neurogenesis in the Brain Ventricular–Subventricular Zone

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1551 ◽  
Author(s):  
Maria Garcia-Garrote ◽  
Ana Perez-Villalba ◽  
Pablo Garrido-Gil ◽  
German Belenguer ◽  
Juan A. Parga ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Functional Dependence ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Receptor Expression ◽  
At2 Receptor ◽  
Angiotensin Type

The renin–angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.

Involvement of AT2 receptors at NRVL in tonic baroreflex suppression by endogenous angiotensins

1997 ◽  
Vol 272 (5) ◽  
pp. H2204-H2210 ◽  
Author(s):  
K. S. Lin ◽  
J. Y. Chan ◽  
S. H. Chan
Keyword(s):  
Suppressive Effect ◽  
Angiotensin Receptors ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Inhibitory Modulation ◽  
Sprague Dawley Rats ◽  
Peptide Antagonist ◽  
Endogenous Activity ◽  
At2 Receptors

We evaluated the role of endogenous angiotensin II and III (ANG II and ANG III) at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved in this process. Adult male Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium were used. Exogenous application of ANG II or ANG III (10, 20, or 40 pmol) by bilateral microinjection into the NRVL significantly suppressed the BRR response to transient hypertension induced by phenylephrine (5 micrograms/kg i.v.). The suppressive effect of ANG II (20 pmol) was reversed by an equimolar dose (1.6 nmol) of its peptide antagonist, [Sar1, Ile8]ANG II, and the nonpeptide antagonists for AT1 and AT2 receptors, losartan and PD-123319, respectively. On the other hand, the inhibitory action of ANG III (20 pmol) was blunted by its peptide antagonist. [Ile7]ANG III or PD-123319, but not by losartan. Blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of [Sar1, Ile8]ANG II, [Ile7]ANG III, or PD-123319 elicited an appreciable enhancement of the BRR response, whereas losartan produced minimal effect. These results suggest that, under physiological conditions, both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the BRR response by acting selectively on the AT2 receptors at the NRVL.

Sign in / Sign up

Export Citation Format

Share Document