Role of the central renin‑angiotensin system in hypertension (Review)

Abstract

Present in more than one billion adults, hypertension is the most significant modifiable risk factor for mortality resulting from cardiovascular disease. Although its pathogenesis is not yet fully understood, the disruption of the renin-angiotensin system (RAS), consisting of the systemic and brain RAS, has been recognized as one of the primary reasons for several types of hypertension. Therefore, acquiring sound knowledge of the basic science of RAS and the under- lying mechanisms of the signaling pathways associated with RAS may facilitate the discovery of novel therapeutic targets with which to promote the management of patients with cardiovascular and kidney disease. In total, 4 types of angiotensin II receptors have been identified (AT1R-AT4R), of which AT1R plays the most important role in vasoconstriction and has been most extensively studied. It has been found in several regions of the brain, and its distribution is highly associated with that of angiotensin-like immunoreactivity in nerve terminals. The effect of AT1R involves the activation of multiple media and signaling pathways, among which the most important signaling pathways are considered to be AT1R/JAK/STAT and Ras/Raf/MAPK pathways. In addition, the regulation of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and cyclic AMP response element-binding (CREB) pathways is also closely related to the effect of ATR1. Their mechanisms of action are related to pro-inflammatory and sympathetic excitatory effects. Central AT1R is involved in almost all types of hypertension, including spontaneous hypertension, salt-sensitive hypertension, obesity-induced hypertension, renovascular hypertension, diabetic hypertension, L-NAME-induced hypertension, stress-induced hypertension, angiotensin II-induced hyper- tension and aldosterone-induced hypertension. There are 2 types of central AT1R blockade, acute blockade and chronic blockade. The latter can be achieved by chemical blockade or genetic engineering. The present review article aimed to high- light the prevalence, functions, interactions and modulation means of central AT-1R in an effort to assist in the treatment of several pathological conditions. The identification of angiotensin-derived peptides and the development of AT-2R agonists may provide a wider perspective on RAS, as well as novel therapeutic strategies.

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension

“…Although the pathogenesis of arterial hypertension is not entirely understood, there is support for the idea that its pathogenesis predominantly consists of a noxious interplay among vascular, renal, neural, and hormonal mechanisms, of which increased activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) prevail [8]; RAAS dysregulation, including the systemic and brain RAAS, has been recognized as one of the main causes of several types of arterial hypertension [9]. RAAS overactivation also contributes to MetS-related obesity and cardiovascular morbidity and mortality [10,11].…”

“…(5) smoking [18]; (6) endothelial dysfunction linked with MetS [19], with excessive release of vasoconstrictive agents and defective secretion of smooth-muscle relaxing mediators, such as nitric oxide [20]; (7) gut microbiota dysbiosis connected with MetS [15,[21][22][23]; (8) inflammatory mechanisms, including pro-inflammatory cytokines and chemokines overexpression, cell infiltration and oxidative stress-all induced by excessive immune system stimulation-that are strongly upregulated in the hypertensive setting [24,25]; (9) innate and adaptive immune system involvement [25,26]; (10) nonalcoholic fatty liver disease (NAFLD), also closely associated with MetS [27]; (11) MetS-related brain neurodegenerative disorders, through disruption to the blood-brain barrier, triggering neuroinflammation, and exacerbation of amyloid disorders and decreased function of the cerebral blood vessels, including reduced cerebral blood flow, altered brain autoregulation, and compromised neurovascular coupling [28][29][30][31]; (12) MetS-related cancer development [32,33].…”

Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

“…Until now, four types of Ang II receptors have been identified (AT1R, AT2R, AT3R, and AT4R) among which the AT1R is the most well studied [ 25 ]. In fact, most Ang II physiological effects are mediated through AT1R [ 14 ].…”

“…In fact, most Ang II physiological effects are mediated through AT1R [ 14 ]. AT1R is a GPCR that requires Ang II binding for its activation [ 14 , 15 , 25 ]. Therefore, it belongs to the canonical seven-transmembrane α-helical superfamily, with an intracellular C-terminal domain, an extracellular N-terminal domain, three intracellular loops (ICL1, ICL 2, ICL3), an amphipathic helix VIII, and three extracellular loops (ECL1, ECL2, ECL3) [ 13 , 14 , 26 ].…”

“…AT1R is expressed in different organs including heart, skin, kidneys, blood vessels, skeletal muscles, brain, liver, lungs, and adrenal glands [ 14 , 25 , 29 ]. Almost all physiological and pathophysiological effects of Ang II are mediated through the AT1R [ 13 ].…”