Regulation of Neuroinflammatory Cytokines by Angiotensin and Cannabinoid Systems in SHR Astrocytes
ISBN or ISSN
The FASEB Journal
Publication Date / Copyright Date
Federation of American Societies for Experimental Biology (FASEB)
To understand the distinct regulatory roles of astroglial cannabinoid and Angiotensin systems, in altering neuroinflammatory states in hypertension.
Neuroinflammation in the brainstem is deemed as a major contributor to neurogenic hypertension. An imbalance in the levels of pro- and anti-inflammatory cytokines, has been reported in the brains of spontaneously hypertensive rats (SHRs). These rats are a model of hypertension and Attention Deficit Hyperactivity Disorder (ADHD). Although cannabinoids exert potent neuroprotective and anti-inflammatory effects, their role in regulation of cytokines in hypertension has not been investigated.
Astrocytes were isolated from the brainstem and cerebellum of Wistar rats and Spontaneously Hypertensive Rat (SHRs) pups. treatments were done with 100 nM Angiotensin (Ang) II or 10 nM of the potent Cannabinoid Type 1 receptor (CB1R) agonist-ACEA, both alone and in combination, for varying time periods, the mRNA and secreted protein levels of interleukin 1 (IL1) and IL10 were measured using qPCR and ELISA, respectively.
Both IL1 and IL10 basal levels were significantly higher in brainstem astrocytes, but not cerebellar astrocytes, of SHRs when compared to normotensive Wistar rat counterparts. Ang II treatment resulted in predominantly elevated IL1 and reduced IL10 levels in both brainstem and cerebellar astrocytes of SHRs and Wistar rats. However, only the Ang II-mediated alterations in IL10 levels was significantly greater in brainstem astrocytes of SHRs when compared to Wistar rats. ACEA treatment on the other hand, was associated with a significant increase in IL10, and a slight reduction in IL1 levels, in both brainstem and cerebellar astrocytes of Wistar rats and SHRs. The effect of ACEA on IL10 was greater in brainstem astrocytes of Wistar rats when compared to SHRs. Co-treatment of Ang II and ACEA resulted in a greater reduction of ACEA-mediated increase in IL-10 in brainstem astrocytes of SHR when compared to Wistar rats.
Significant differences in basal cytokine levels in brainstem astroglial cultures from SHRs and Wistar rats, indicates a dysregulated neuroinflammatory state in brainstem astrocytes under hypertensive conditions. Greater IL10 elevation, by ACEA, in brainstem astrocytes of Wistar rats when compared to SHRs, is indicative of endocannabinoid hypofunction in hypertension. The inability of CB1R to elicit a protective role in brainstem astrocytes under hypertensive states, could well be an important facet in the etiology of essential hypertension.
Support or Funding Information
NSU HPD: Grant # 335585
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
angiotensin, astrocytes, cannabinoid systems, cytokines
Giridhar, Dhanush Haspula and Clark, Michelle A., "Regulation of Neuroinflammatory Cytokines by Angiotensin and Cannabinoid Systems in SHR Astrocytes" (2017). Faculty Articles. 317.