Faculty Articles

Angiotensin II Induces Cyclooxygenase 2 Expression in Rat Astrocytes via the Angiotensin Type 1 Receptor

Publication Title

Neuropeptides

Volume

77

Publication Date / Copyright Date

10-1-2019

Abstract

We previously showed that Angiotensin (Ang) II stimulated pro-inflammatory and mitogenic actions in astrocytes suggesting that astrocytes are emerging as key players in neuroinflammation. Evidence suggests that neuroinflammation may contribute to central sympathetic overactivity and elevated blood pressure. Further, cyclooxygenase (Cox)-derived prostanoids were implicated in Ang II-dependent hypertension. Cox2 is one of two Cox isoenzymes that is responsible for the formation of prostanoids from arachidonic acid. Constitutively expressed Cox2 has a protective and homeostatic role in the cardiovascular and renal systems. Inducible Cox2 has been associated with pathogenic stimuli resulting in inflammatory conditions and cancers. In this study, we investigated the effect of Ang II on Cox2 protein and mRNA expression in brainstem and cerebellum astrocytes, and determined whether any differences in Cox2 expression exist in spontaneously hypertensive rat (SHR) astrocytes compared to their normotensive control Wistar rats. We demonstrated that Ang II increased Cox2 protein and mRNA levels relative to untreated controls in a time-dependent manner, in Wistar and SHR brainstem and cerebellum astrocytes. Increases in Cox2 protein expression were evident within 4 h, with subsequent sustained elevation for several hours followed by a decline at 48 h. Ang II-induced Cox2 protein levels were higher in Wistar compared to SHRs in both brainstem and cerebellum astrocytes for the majority of time points examined. The Ang II-induced Cox2 mRNA levels increased within 8 h followed by a rapid decline to almost basal levels at later time points. At the earlier time points, Cox2 mRNA elevation were higher in SHR compared to Wistar rat astrocytes. These Ang II actions were mediated by the Ang type I receptor. Our results corroborate previous reports of Ang II's ability to stimulate neuroinflammatory mediators in astrocytes. Cox2-derived prostaglandins might play a role in brain-renin angiotensin system associated hypertension, and astrocytes could be significant players.

Disciplines

Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences

Keywords

angiotensin II, angiotensin type 1 receptor, astrocytes, cyclooxygenase 2, spontaneously hypertensive rat

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