RT Journal Article
SR Electronic
T1 Molecular basis of brain RAS in cardiovascular and neurological disorders: Uncovering a key role for the astroglial AT1R
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.118.248831
DO 10.1124/jpet.118.248831
A1 Dhanush Haspula
A1 Michelle A. Clark
YR 2018
UL http://jpet.aspetjournals.org/content/early/2018/05/11/jpet.118.248831.abstract
AB The central renin angiotensin system (RAS) is one of the most widely investigated cardiovascular systems in the brain. It is implicated in a myriad of cardiovascular diseases. However, studies from the last decade have identified its involvement in several neurological abnormalities. Understanding the molecular functionality of the various RAS components can thus provide considerable insight into the phenotypic differences and mechanistic drivers of not just cardiovascular, but also neurological disorders. Since activation of one of its primary receptors, the angiotensin type-1 receptor (AT1R) results in an augmentation of oxidative stress and inflammatory cytokines, it becomes essential to investigate not just neuronal RAS, but also glial RAS as well. Glial cells are key homeostatic regulators in the brain, and are critical players in the resolution of overt oxidative stress and neuroinflammation. Designing better and effective therapeutic strategies that target the brain RAS, could well hinge on understanding the molecular basis of both neuronal and glial RAS. This review provides a comprehensive overview of the major studies that have investigated the mechanisms and regulation of brain RAS, and it also provides insight into the potential role of glial AT1Rs in the pathophysiology of cardiovascular and neurological disorders.