scholarly journals μ-Opioid Receptor-Mediated AT1R–TLR4 Crosstalk Promotes Microglial Activation to Modulate Blood Pressure Control in the Central Nervous System

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1784
Author(s):  
Gwo-Ching Sun ◽  
Jockey Tse ◽  
Yung-Ho Hsu ◽  
Chiu-Yi Ho ◽  
Ching-Jiunn Tseng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Binding ◽  
Peptide Hormone ◽  
Pressure Control ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
The Central Nervous System ◽  
Μ Opioid Receptor ◽  
Cerebral Inflammation

Opioids, a kind of peptide hormone involved in the development of hypertension, cause systemic and cerebral inflammation, and affects regions of the brain that are important for blood pressure (BP) control. A cause-and-effect relationship exists between hypertension and inflammation; however, the role of blood pressure in cerebral inflammation is not clear. Evidence showed that AT1R and μOR heterodimers’ formation in the NTS might lead to the progression of hypertension. In this study, we investigated the formation of the μOR/AT1R heterodimer, determined its correlation with μORs level in the NTS, and explored the role of TLR4-dependent inflammation in the development of hypertension. Results showed that Ang II increased superoxide and Iba-1 (microgliosis marker: ionized calcium-binding adaptor molecule (1) levels in the NTS of spontaneously hypertensive rats (SHRs). The AT1R II inhibitor, losartan, significantly decreased BP and abolished superoxide, Iba-1, TLR4 expression induced by Ang II. Furthermore, losartan significantly increased nNsOSS1416 phosphorylation. Administration of a μOR agonist or antagonist in the NTS of WKY and SHRs increased endogenous μ-opioids, triggered the formation of μOR/AT1R heterodimers and the TLR4-dependent inflammatory pathway, and attenuated the effect of depressor nitric oxide (NO). These results imply an important link between neurotoxicity and superoxides wherein abnormal increases in NTS endogenous μ-opioids promote the interaction between Ang II and μOR, the binding of Ang II to AT1R, and the activation of microglia. In addition, the interaction between Ang II and μOR enhanced the formation of the AT1R and μOR heterodimers, and inactivated nNOS-derived NO, leading to the development of progressive hypertension.

Role of Vasopressin in Blood Pressure Control of Spontaneously Hypertensive Rats

1978 ◽  
Vol 55 (s4) ◽  
pp. 247s-250s ◽  
Author(s):  
Jan Möhring ◽  
Jacqueline Kintz ◽  
Josiane Schoun
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Spontaneously Hypertensive Rats ◽  
Salt Intake ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High Salt Intake

1. The role of arginine—vasopressin (AVP) and of angiotensin in blood pressure control of spontaneously hypertensive rats (SH rats, stroke-prone strain) was studied. 2. In SH rats, which drank water or 1% NaCl, plasma AVP concentrations were elevated during the benign course of hypertension and increased further when the animals entered the malignant phase. Blood pressure correlated significantly with plasma AVP concentrations in SH rats on water, but not in SH rats on saline. 3. The injection of a specific AVP antiserum lowered blood pressure significantly in SH rats on water and in SH rats on saline. 4. When the correlation between blood pressure and plasma AVP of SH rats on water was compared with the respective correlation obtained during infusion of AVP into normotensive rats, a marked shift to the left became apparent, the factor of displacement amounting to more than 1000. 5. Saralasin did not affect blood pressure of SH rats on water, except for two rats with malignant hypertension. However, in SH rats on saline, saralasin lowered blood pressure significantly. 6. It is concluded that in SH rats AVP plays an important vasopressor role in blood pressure control and that sensitization to the vasopressor effect of AVP occurs in these animals. The renin—angiotensin system is significantly involved in blood pressure control of SH rats only when they are subjected to high salt intake.

Angiotensin II inhibits DDAH1–nNOS signaling via AT1R and μOR dimerization to modulate blood pressure control in the central nervous system

2019 ◽  
Vol 133 (23) ◽  
pp. 2401-2413 ◽  
Author(s):  
Gwo-Ching Sun ◽  
Tzyy-Yue Wong ◽  
Hsin-Hung Chen ◽  
Chiu-Yi Ho ◽  
Tung-Chen Yeh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Drug Targets ◽  
Nucleus Tractus Solitarius ◽  
Pressure Control ◽  
No Production ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Extracellular Signal ◽  
Wistar Kyoto

Abstract G protein-coupled receptors (GPCRs) are important drug targets. Blocking angiotensin II (Ang II) type 1 receptor signaling alleviates hypertension and improves outcomes in patients with heart failure. Changes in structure and trafficking of GPCR, and desensitization of GPCR signaling induce pathophysiological processes. We investigated whether Ang II, via induction of AT1R and μ-opioid receptor (μOR) dimerization in the nucleus tractus solitarius (NTS), leads to progressive hypertension. Ang II signaling increased μOR and adrenergic receptor α2A (α2A-AR) heterodimer levels and decreased expression of extracellular signal-regulated kinases 1/2T202/Y204, ribosomal protein S6 kinaseT359/S363, and nNOSS1416 phosphorylation. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) expression was abolished in the NTS of adult spontaneously hypertensive rats (SHRs). Endomorphin-2 was overexpressed in NTS of adult SHRs compared with that in 6-week-old Wistar-Kyoto rats (WKY). Administration of μOR agonist into the NTS of WKY increased blood pressure (BP), decreased nitric oxide (NO) production, and decreased DDAH1 activity. μOR agonist significantly reduced the activity of DDAH1 and decreased neuronal NO synthase (nNOS) phosphorylation. The AT1R II inhibitor, losartan, significantly decreased BP and abolished AT1R-induced formation of AT1R and μOR, and α2A-AR and μOR, heterodimers. Losartan also significantly increased the levels of nNOSS1416 phosphorylation and DDAH1 expression. These results show that Ang II may induce expression of endomorphin-2 and abolished DDAH1 activity by enhancing the formation of AT1R and μOR heterodimers in the NTS, leading to progressive hypertension.

scholarly journals Role of Mineralocorticoid and Angiotensin Type 1 Receptors in the Paraventricular Nucleus in Angiotensin-Induced Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Sandra L. Burke ◽  
Benjamin Barzel ◽  
Kristy L. Jackson ◽  
Cindy Gueguen ◽  
Morag J. Young ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Paraventricular Nucleus ◽  
Pressure Control ◽  
Treated Group ◽  
Inhibitory Influence ◽  
Ang Ii ◽  
Air Jet

The hypothalamic paraventricular nucleus (PVN) is an important site where an interaction between circulating angiotensin (Ang) and mineralocorticoid receptor (MR) activity may modify sympathetic nerve activity (SNA) to influence long-term elevation of blood pressure. We examined in conscious Ang II-treated rabbits, the effects on blood pressure and tonic and reflex renal SNA (RSNA) of microinjecting into the PVN either RU28318 to block MR, losartan to block Ang (AT1) receptors or muscimol to inhibit GABAA receptor agonist actions. Male rabbits received a moderate dose of Ang II (24 ng/kg/min subcutaneously) for 3 months (n = 13) or sham treatment (n = 13). At 3 months, blood pressure increased by +19% in the Ang II group compared to 10% in the sham (P = 0.022) but RSNA was similar. RU28318 lowered blood pressure in both Ang II and shams but had a greater effect on RSNA and heart rate in the Ang II-treated group (P < 0.05). Losartan also lowered RSNA, while muscimol produced sympatho-excitation in both groups. In Ang II-treated rabbits, RU28318 attenuated the blood pressure increase following chemoreceptor stimulation but did not affect responses to air jet stress. In contrast losartan and muscimol reduced blood pressure and RSNA responses to both hypoxia and air jet. While neither RU28318 nor losartan changed the RSNA baroreflex, RU28318 augmented the range of the heart rate baroreflex by 10% in Ang II-treated rabbits. Muscimol, however, augmented the RSNA baroreflex by 11% in sham animals and none of the treatments altered baroreflex sensitivity. In conclusion, 3 months of moderate Ang II treatment promotes activation of reflex RSNA principally via MR activation in the PVN, rather than via activation of AT1 receptors. However, the onset of hypertension is independent of both. Interestingly, the sympatho-excitatory effects of muscimol in both groups suggest that overall, the PVN regulates a tonic sympatho-inhibitory influence on blood pressure control.

Heat shock proteins 27 and 70 regulating angiotensin II-induced NF-κB: a possible connection to blood pressure control?

2008 ◽  
Vol 33 (5) ◽  
pp. 1042-1049 ◽  
Author(s):  
Tracy S. Voegeli ◽  
Amanda J. Wintink ◽  
Yu Chen ◽  
R. William Currie
Keyword(s):  
Blood Pressure ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Pressure Control ◽  
Nuclear Factor ◽  
Ang Ii ◽  
Regulate Protein ◽  
Shock Proteins ◽  
Transcription Factor Nuclear Factor

Heat shock proteins (HSPs) are critical for cell survival and have several mechanisms of action. HSPs regulate protein folding, suppress apoptosis, and regulate anti-oxidative activity. In addition, HSPs are involved in the regulation of the pro-inflammatory transcription factor nuclear factor (NF)-κB. When angiotensin (Ang) II is infused into rats, there is a significant increase in systolic blood pressure, and NF-κB is activated in the heart. If rats are heat shocked to induce the heat shock response and HSPs before Ang II infusion, there is a significant suppression of both the Ang II-induced increase in blood pressure and NF-κB activation in the heart. Although the role of specific HSPs in the regulation of NF-κB is unclear, several HSPs, including Hsp27 and Hsp70, are thought to be involved in the regulation of Ang II-induced NF-κB. The role of Hsp27 and Hsp70 in NF-κB activation is reviewed here, along with evidence suggesting that HSPs regulate Ang II-induced blood pressure through the regulation of NF-κB.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin

1980 ◽  
Vol 59 (s6) ◽  
pp. 235s-237s ◽  
Author(s):  
R. W. Rockhold ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Hypertensive Rats ◽  
Methionine Enkephalin ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.

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