Brain angiotensin type-1 and type-2 receptors: cellular locations under normal and hypertensive conditions

The counter regulatory axis of the renin angiotensin system in the brain and ischaemic stroke: Insight from preclinical stroke studies and therapeutic potential

“…Furthermore, expression of the RAS components has been demonstrated within the brain, with renin activity demonstrated in the brain independent of circulating renin [ 67 ], angiotensinogen mRNA detected across the rat brain [ 68 ] and in both astrocytes [ 69 ] and neurons [ 70 ], ACE detected by radioligand binding in various regions of the human brain [ 71 ], and detection of Ang II and other angiotensin peptides (including Ang-(1–9) and Ang-(1–7)) in rat and sheep brains [ 72 ]. Following the discovery of ACE2, its expression was also confirmed within the brain at both a mRNA and protein level [ 73 ], and expression of the RAS receptors, AT 1 R, AT 2 R and Mas receptor, in the brain have been demonstrated by numerous studies [ [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] ]. Recently, however, the existence of a locally expressed brain RAS has been questioned when van Thiel et al .…”

“…Its expression is highest in fetal tissues and declines after birth [ 169 ] although more recently this concept was challenged with a study showing higher levels of AT 2 R protein in brainstem, liver and kidney in adult rats compared to fetal or neonatal rats [ 170 ]. The gene coding for AT 2 R has been mapped to the X chromosome [ 171 ] and studies in rodents have indicated a higher expression of AT 2 R in females compared to males due to upregulation by estrogen in the brain and heart [ 172 , 173 ], however, others have recently reported no overall sex related differences in AT 2 R, or AT 1 R, expression in the mouse brain [ 82 ]. Other regulators of AT 2 R expression include glucocorticoids and cytokines [ 174 ] or specifically, the nuclear protein poly(ADP-ribose) polymerase-1 (PARP1) [ 175 ] or transcription factor promyelocytic zinc finger protein (PLZF) [ 176 ] which regulate AT 2 R transcription.…”

Interactions of the Brain Renin-Angiotensin-System (RAS) and Inflammation in the Sensitization of Hypertension

“…Besides a prohypertensive axis of the RAS, an antihypertensive axis of the RAS has also been identified and studied extensively regarding its protective role in the development of hypertension ( Xu et al, 2011 ; Medina and Arnold, 2019 ; Sumners et al, 2020 ). This review also will discuss briefly recent evidence describing the protective effects of the RAS antihypertensive axis on HTRS.…”

“…The so-called brain RAS is associated with neurons, astrocytes and microglia functions in a paracrine, autocrine, and even intracrine signaling role ( Huber et al, 2017 ; Jackson et al, 2018 ; Nakagawa et al, 2020 ). Many CNS nuclei (i.e., the LT, PVN, RVLM, NTS and AP) implicated in cardiovascular control and fluid balance are rich in AT1-R-positive cells and are often innervated by axons containing some components of the RAS ( Sumners et al, 2020 ).…”

“…Recent studies demonstrate that either AT2-R or ACE2/ANG-(1-7)/Mas-R are present either within or adjacent to cardiovascular nuclei in the brainstem and hypothalamus that express the AT1-R ( Gao and Zucker, 2011 ; Gao et al, 2012 ; Sumners et al, 2015 , 2020 ; Medina and Arnold, 2019 ). Functionally, in contrast to the prohypertensive effects of brain AT1-R activation to increase sympathetic activity and BP, either overexpression or selective activation of central AT2-R decreases BP and plasma norepinephrine levels at least partially by reducing sympathetic outflow ( Gao et al, 2008 , 2011 ).…”