The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system. A decrease in the dopaminergic function induces upregulation of the angiotensin type-1 (AT1) receptor activity, leading to recovery of dopamine levels. However, AT1 receptor overactivity in dopaminergic neurons and microglial cells upregulates the cellular NADPH-oxidase-superoxide axis and Ca release, which mediate several key events in oxidative stress, neuroinflammation, and α-synuclein aggregation, involved in Parkinson's disease (PD) pathogenesis. An intraneuronal antioxidative/anti-inflammatory RAS counteracts the effects of the pro-oxidative AT1 receptor overactivity. Consistent with this, an imbalance in RAS activity towards the pro-oxidative/pro-inflammatory AT1 receptor axis has been observed in the substantia nigra and striatum of several animal models of high vulnerability to dopaminergic degeneration. Interestingly, autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors are increased in PD models and PD patients and contribute to blood-brain barrier (BBB) dysregulation and nigrostriatal pro-inflammatory RAS upregulation. Therapeutic strategies addressed to the modulation of brain RAS, by AT1 receptor blockers (ARBs) and/or activation of the antioxidative axis (AT2, Mas receptors), may be neuroprotective for individuals with a high risk of developing PD or in prodromal stages of PD to reduce progression of the disease.
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http://dx.doi.org/10.1186/s40035-024-00410-3 | DOI Listing |
Utilizing data from the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) Trial, this hub model was developed to limit seventeen Renin-Angiotensin-Aldosterone System (RAAS) components as three entrance and four exits, to facilitate the calculation of a model as one egress unknown, the angiotensin type 1 (AT1) receptor. Following previous evidence relating renin levels to mortality, this study found controls were more like sepsis patients with levels < renin quartile 1 (Q1) for calculated AT1, while more like sepsis patients with renin levels > quartile 3 (Q4) for measured aldosterone levels. Additionally differential discrete correlate summation (DCS) analysis indicates AT1, aldosterone and renin as major hub nodes in this independent DCS model of metabolic data inputs.
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Department of Oral Biology, Semmelweis University, H-1089 Budapest, Hungary.
NMDA receptors in the prefrontal cortex (PFC) play a crucial role in cognitive functions. Previous research has indicated that angiotensin II (Ang II) affects learning and memory. This study aimed to examine how Ang II impacts NMDA receptor activity in layer V pyramidal cells of the rat PFC.
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Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, GA 31404, USA.
Heart failure is a complex syndrome characterized by cardiac hypertrophy, fibrosis, and diastolic/systolic dysfunction. These changes share many pathological features with significant inflammatory responses in the myocardium. Among the various regulatory systems that impact on these heterogeneous pathological processes, angiotensin II (Ang II)-activated macrophages play a pivotal role in the induction of subcellular defects and cardiac adverse remodeling during the progression of heart failure.
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School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, P. R. China.
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Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
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