The phosphoinositide‐3 kinase signaling is involved in neuroinflammation in hypertensive rats

Tan, Xing; Jiao, Pei-Lei; Wang, Yang-Kai; Wu, Zhao-Tang; Zeng, Xiaorong; Li, Miaoling; Wang, Weizhong

doi:10.1111/cns.12679

Cited by 26 publications

(16 citation statements)

References 41 publications

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“…Based on the above research evidence, we speculate that β-arrestin1 may activate Nrf2 through PI3K/Akt or ERK signaling pathways, thereby exerting its antioxidative stress effect. However, combined with the results of our previous study ( Tan et al, 2017 ), the PI3K/Akt pathway in the RVLM of hypertensive rats was activated, and inhibition of the PI3K/Akt pathway ameliorated neuroinflammation, thereby reducing BP. Given that the PI3K/Akt pathway mediates neuroinflammation and promotes the occurrence of hypertension, overexpression of β-arrestin1 exerts an antihypertensive effect through Nrf2 activation.…”

Section: Discussionsupporting

confidence: 60%

β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension

et al. 2021

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Oxidative stress in the rostral ventrolateral medulla (RVLM), a key region for blood pressure (BP) regulation, has been demonstrated to be responsible for the overactivity of the sympathetic nervous system in hypertension and heart failure. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is a key transcription factor that maintains redox homeostasis by governing a broad array of antioxidant genes in response to oxidative stress. β-Arrestin1 is a multifunctional scaffold protein with the ability to interact with diverse signaling molecules independent of G protein-coupled receptors (GPCRs), and its overexpression in the RVLM could reduce BP and renal sympathetic nerve activity (RSNA) in spontaneously hypertensive rats (SHR). The goal of this study was to investigate whether Nrf2-mediated antioxidative stress is involved in the antihypertensive effect of β-arrestin1 in the RVLM. It was found that the activation level of Nrf2 in the RVLM of SHR was significantly reduced, compared with normotensive Wistar-Kyoko (WKY) rats. Overexpression of β-arrestin1 in the RVLM significantly decreased ROS production and facilitated the Nrf2 activation in the RVLM of SHR, accompanied by upregulating the expression of HO-1 and NQO-1. However, Nrf2 knockdown attenuated the antioxidant effect of β-arrestin1 overexpression in the RVLM by downregulating HO-1 and NQO-1 expression levels. In conclusion, the current results suggested that the antihypertensive effect of β-arrestin1 overexpression in the RVLM is mediated by decreased ROS production, which is associated with Nrf2 activation.

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Section: Discussionsupporting

confidence: 60%

β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension

et al. 2021

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“…These findings in human are in line with previous studies in rodents showing lower systolic blood pressure due mainly to a more prominent baroreflex afferent function in adult female rats . The obvious question has been why females demonstrate a higher parasympathetic activity when compared to males . It can be explained partly by the female‐specific distribution of myelinated Ah‐type baroreceptor/baroreceptive neurons in both NG and NTS likely due to their relatively higher parasympathetic activity at cellular level .…”

Section: Discussionsupporting

confidence: 90%

Spontaneous activities in baroreflex afferent pathway contribute dominant role in parasympathetic neurocontrol of blood pressure regulation

Feng

et al. 2018

CNS Neurosci Ther

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“…It is known that the state of oxidation is higher in the RVLM under hypertension. Our previous work also determined that ACE2 overexpression decreases the level of neuroinflammation in the RVLM [ 22 ]. So whether the nAChRs involved in the neuroprotective effect of ACE2 overexpression is still unknown and needs further study.…”

Section: Discussionmentioning

confidence: 99%

“…The processes of cloning human hACE2 into lentiviral vector and the construction of Lenti-ACE2 were as follows. The Lenti-ACE2 virus particles were packaged by Shanghai Innovation Biotechnology Ltd. (Shanghai, China), following the description in our previous study [ 22 ]. hACE2 cDNA (Accession No.…”

Section: Methodsmentioning

confidence: 99%

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Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Regulates Cholinergic Signaling and Cardiovascular and Sympathetic Responses in Hypertensive Rats

Deng

Tan

et al. 2018

Neurosci. Bull.

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The rostral ventrolateral medulla (RVLM) is a key region in cardiovascular regulation. It has been demonstrated that cholinergic synaptic transmission in the RVLM is enhanced in hypertensive rats. Angiotensinconverting enzyme 2 (ACE2) in the brain plays beneficial roles in cardiovascular function in hypertension. The purpose of this study was to determine the effect of ACE2 overexpression in the RVLM on cholinergic synaptic transmission in spontaneously hypertensive rats (SHRs). Four weeks after injecting lentiviral particles containing enhanced green fluorescent protein and ACE2 bilaterally into the RVLM, the blood pressure and heart rate were notably decreased. ACE2 overexpression significantly reduced the concentration of acetylcholine in microdialysis fluid from the RVLM and blunted the decrease in blood pressure evoked by bilateral injection of atropine into the RVLM in SHRs. In conclusion, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced cholinergic synaptic transmission in SHRs.

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The phosphoinositide‐3 kinase signaling is involved in neuroinflammation in hypertensive rats

Abstract: This study suggests that the PI3K signaling in the RVLM is involved in neuroinflammation in hypertension and plays an important role in the renin-angiotensin system-mediated changes in neuroinflammation in the RVLM.

Cited by 26 publications

References 41 publications

β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension

β-Arrestin1 Reduces Oxidative Stress via Nrf2 Activation in the Rostral Ventrolateral Medulla in Hypertension

Spontaneous activities in baroreflex afferent pathway contribute dominant role in parasympathetic neurocontrol of blood pressure regulation

Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Regulates Cholinergic Signaling and Cardiovascular and Sympathetic Responses in Hypertensive Rats

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