Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation

Abstract

The renin-angiotensin system (RAS) is a fundamental regulator of blood pressure and has emerged as an important player in the control of inflammatory processes. Accordingly, imbalance on RAS components either systemically or locally might trigger the development of inflammatory disorders by affecting immune cells. At the same time, alterations in the dopaminergic system have been consistently involved in the physiopathology of inflammatory disorders. Accordingly, the interaction between the RAS and the dopaminergic system has been studied in the context of inflammation of the central nervous system (CNS), kidney, and intestine, where they exert antagonistic actions in the regulation of the immune system. In this review, we summarized, integrated, and discussed the cross talk of the dopaminergic system and the RAS in the regulation of inflammatory pathologies, including neurodegenerative disorders, such as Parkinson's disease. We analyzed the molecular mechanisms underlying the interaction between both systems in the CNS and in systemic pathologies. Moreover, we also analyzed the impact of the commensal microbiota in the regulation of RAS and dopaminergic system and how it is involved in inflammatory disorders. Furthermore, we summarized the therapeutic approaches that have yielded positive results in preclinical or clinical studies regarding the use of drugs targeting the RAS and dopaminergic system for the treatment of inflammatory conditions. Further understanding of the molecular and cellular regulation of the RAS-dopaminergic cross talk should allow the formulation of new therapies consisting of novel drugs and/or repurposing already existing drugs, alone or in combination, for the treatment of inflammatory disorders.

The Impact of Some Modulators of the Renin–Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model

“…Due to LOS effects on the blood–brain barrier permeability modulation, as [ 34 ] showed in a rat model of angiotensin-II-induced arterial hypertension, LOS could also exhibit modulatory effects on the brain tissues. Thus, we previously showed that RAS modulation using LOS and RAM could improve cognitive performances and socio-affective behavior, while Abiodun and Ola [ 35 ] and Campos and Pacheco [ 36 ] provided an updated perspective of the RAS system in neurodegeneration and inflammation. Moreover, Ahmed et al [ 37 ] and Mirzahosseini et al [ 38 ] even described promising mechanisms in which RAS modulation could prevent progressive cognitive impairments and inflammation following brain-injury-derived neurodegeneration.…”

α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect

“…The high levels of dopamine, ranging from 1 to 10 μM, in vivo binding to low-affinity dopamine receptors (DRD1 and DRD2) on microglia could exert anti-inflammatory effects by modulating the proinflammatory renin–angiotensin system [ 108 , 109 ], and DRD1 could mediate the autophagic degradation of NLRP3 protein. The low levels of dopamine in the body, ranging from 20 to 500 nM, could selectively stimulate the high-affinity dopamine receptors (DRD3, DRD4, and DRD5), thereby inducing inflammatory responses [ 110 ].…”

AT1 receptor autoantibodies mediate effects of metabolic syndrome on dopaminergic vulnerability

“…Previous studies from our laboratory and others have involved the brain renin-angiotensin system (RAS) in progression of Parkinson's disease and other neurodegenerative diseases by enhancing neuronal oxidative stress and neuroinflammatory processes (Campos and Pacheco, 2020;Labandeira-Garcia et al, 2013;Labandeira-Garcia et al, 2017;Wright and Harding, 2019). Interestingly (Labandeira-Garcia and Parga, 2022), a recent study has shown that the population of human dopaminergic neurons most vulnerable to degeneration in Parkinson's disease can be identified by their high expression of angiotensin type-1 (AT1) gen (Kamath et al, 2022).…”