Effect of Ang II on angiotensinogen expression levels in hypertensive rat astrocytes (1140.1)

Abstract

Objective: To investigate the effects of Angiotensin II (Ang II) on Angiotensinogen (AGT) mRNA and protein levels in spontaneous hypertensive rats (SHR) astrocytes. Background: AGT is the precursor molecule for the synthesis of Ang II produced by the renin angiotensin system (RAS). Astrocytes are the major source of AGT in the brain, and regulation of brain AGT levels alters blood pressure and electrolyte homeostasis. In this study, SHR were used as a genetic hypertension model and the results were compared to normotensive Wistar rats. Methods: Astrocytes isolated from neonatal rat’s cerebellum (CB) and brainstem (BS) regions were treated with 100nM Ang II, and the time‐dependent effect of Ang II on AGT protein and mRNA levels were measured using Western blotting and quantitative polymerase chain reaction techniques, respectively. Results: Ang II significantly increased AGT protein levels but, decreased AGT mRNA levels over most time points examined in BS and CB Wistar and SHR astrocytes. There was no significant difference between Ang II’s ability to affect AGT protein and mRNA levels in SHR as compared to Wistar astrocytes. Conclusions: These findings showed that Ang II regulates it’s synthesis by inducing basal AGT protein and mRNA levels. Further, the ability of astrocytes to produce AGT may not be contributing to the hypertensive state in the SHR model. Grant Funding Source: Supported by Nova Southeastern University Chancellor's Faculty Research & Development Grant # 335872