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

Autor: Miao-Ling Li, Xiao-Rong Zeng, Wei-Zhong Wang, Wang Yangkai, Zhao-Tang Wu, Pei-Lei Jiao, Tan Xing
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Lipopolysaccharides
Male
medicine.medical_specialty
Sympathetic Nervous System
Blood Pressure
030204 cardiovascular system & hematology
Peptidyl-Dipeptidase A
Rats
Inbred WKY
Proinflammatory cytokine
03 medical and health sciences
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Heart Rate
Physiology (medical)
Internal medicine
Rats
Inbred SHR
Gene silencing
Medicine
Animals
Humans
Pharmacology (medical)
RNA
Small Interfering
PI3K/AKT/mTOR pathway
Neuroinflammation
Pharmacology
Medulla Oblongata
Phosphoinositide 3-kinase
biology
Dose-Response Relationship
Drug
business.industry
Angiotensin II
Rostral ventrolateral medulla
Original Articles
Rats
Psychiatry and Mental health
Endocrinology
P110δ
Hypertension
biology.protein
Cytokines
Encephalitis
Angiotensin-Converting Enzyme 2
business
030217 neurology & neurosurgery
Signal Transduction
Popis: SummaryAims It has been demonstrated that neuroinflammation is associated with cardiovascular dysfunction. The phosphoinositide-3 kinase (PI3K) signaling in the rostral ventrolateral medulla (RVLM), a key region for sympathetic outflow, is upregulated and contributes to increased blood pressure (BP) and sympathetic outflow in hypertension. This study was designed to determine the role of the PI3K signaling in neuroinflammation in the RVLM of hypertension. Methods The normotensive WKY rats were performed by intracisternal infusion of lipopolysaccharide (LPS) or angiotensin II (Ang II) for inducing neuroinflammation. Elisa was used to determine the level of proinflammatory cytokines. Western blot was employed to detect the protein expression of PI3K signaling pathway. Gene silencing of PI3K p110δ subunit and overexpression of angiotensin-converting enzyme 2 (ACE2) were realized by injecting related lentivirus into the RVLM. Results In the spontaneously hypertensive rats (SHR), the PI3K signaling in the RVLM was upregulated compared with WKY, gene silencing of PI3K in the RVLM significantly reduced BP and renal sympathetic nerve activity (RSNA), but also decreased the levels of proinflammatory cytokines. In the WKY rats, central infusion of LPS and Ang II significantly elevated BP and RSNA, but also increased the levels of proinflammatory cytokines and PI3K signaling activation in the RVLM. These changes in the Ang II-induced hypertension were effectively prevented by gene silencing of PI3K in the RVLM. Furthermore, overexpression of ACE2 in the RVLM significantly attenuated high BP and neuroinflammation, as well as decreased the activation of PI3K signaling in hypertensive rats. Conclusion 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.
Databáze: OpenAIRE
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