New therapeutic pathways in the RAS

Bäder, Michael; Santos, Robson A.S.; Unger, Thomas; Steckelings, Ulrike Muscha

doi:10.1177/1470320312466519

Cited by 35 publications

(42 citation statements)

References 22 publications

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“…Several different strategies have been developed to directly activate this receptor or to increase the concentration of its main agonist, Ang-(1-7), and some have already entered clinical trials (Steckelings et al, 2011;Bader et al, 2012;Ferreira et al, 2012). However, none is already approved for therapy.…”

Section: Discussionmentioning

confidence: 99%

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

et al. 2014

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“…The heptapeptide, ANG-(1-7), is the substrate by the action mainly of angiotensin-converting enzyme II (ACE2) cleaving ANG II. Acting preferentially in the Mas receptor, ANG-(1-7) has been shown as a new pharmacological target to ameliorate the course of cardiovascular, renal, immunological, and neurological diseases in experimental models (3,60).Several previous studies indicate that peptides of the RAS may act in the brain regulating a number of physiological processes (28, 31). In particular, the brain ACE, ANG II, and AT 1 receptor has been reported to have an important role in cardiovascular regulation under stress condition (2).…”

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confidence: 98%

Activation of angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis attenuates the cardiac reactivity to acute emotional stress

Lima

Xavier

Ferreira

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Recent data indicate the brain angiotensin-converting enzyme/ANG II/AT1 receptor axis enhances emotional stress responses. In this study, we investigated whether its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/ANG-(1-7)/Mas axis, attenuate the cardiovascular responses to acute emotional stress. In conscious male Wistar rats, the tachycardia induced by acute stress (air jet 10 l/min) was attenuated by intravenous injection of ANG-(1-7) [Δ heart rate (HR): saline 136 ± 22 vs. ANG-(1-7) 61 ± 25 beats/min; P < 0.05]. Peripheral injection of the ACE2 activator compound, XNT, abolished the tachycardia induced by acute stress. We found a similar effect after intracerebroventricular injections of either ANG-(1-7) or XNT. Under urethane anesthesia, the tachycardia evoked by the beta-adrenergic agonist was markedly reduced by ANG-(1-7) [ΔHR: saline 100 ± 16 vs. ANG-(1-7) 18 ± 15 beats/min; P < 0.05]. The increase in renal sympathetic nerve activity (RSNA) evoked by isoproterenol was also abolished after the treatment with ANG-(1-7) [ΔRSNA: saline 39% vs. ANG-(1-7) -23%; P < 0.05]. The tachycardia evoked by disinhibition of dorsomedial hypothalamus neurons, a key nucleus for the cardiovascular response to emotional stress, was reduced by ∼45% after intravenous injection of ANG-(1-7). In cardiomyocyte, the incubation with ANG-(1-7) (1 μM) markedly attenuated the increases in beating rate induced by isoproterenol. Our data show that activation of the ACE2/ANG-(1-7)/Mas axis attenuates stress-induced tachycardia. This effect might be either via the central nervous system reducing anxiety level and/or interfering with the positive chronotropy mediated by activation of cardiac β adrenergic receptors. Therefore, ANG-(1-7) might contribute to reduce the sympathetic load to the heart during situations of emotional stress, reducing the cardiovascular risk.

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“…15 On the other hand, stimulation of the angiotensin type 2 (AT 2 ) receptor, which has been expected to play a protective role in RAS. 16,17 by a direct agonist, compound 21 (C21), decreased dopamine synthesis in the rat striatum. 18 Moreover, a previous in vitro study also demonstrated that stimulation of the AT 2 receptor reduced catecholamine biosynthesis via a decrease in cGMP level in adrenal medullary cells.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II type 2 receptor signaling affects dopamine levels in the brain and prevents binge eating disorder

Nakaoka

Mogi

Kanno

et al. 2015

J Renin Angiotensin Aldosterone Syst

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Introduction: Binge eating disorder (BED) is associated with dopaminergic activation as food reward, resulting in metabolism-related disorders. Stimulation of angiotensin type 2 (AT2) receptor is reported to inhibit dopamine synthesis. We investigated the possible roles of AT2 receptor-mediated dopamine regulation in the pathogenesis of BED. Materials and methods: Male C57BL/6 mice, type 2 diabetic (KKAy) mice and AT2 receptor-null (AT2KO) mice at eight weeks old were treated with AT2 receptor agonist, compound 21 (C21) or saline for two weeks. Mice were subjected to fasting for two days followed by re-feeding for seven days. Results: Treatment with C21 attenuated the rebound proportion of body weight, food intake and water intake in KKAy mice, but not in C57BL/6 and AT2KO mice. Dopamine concentration in the striatum was further increased by fasting in KKAy and AT2KO mice. Administration of C21 significantly attenuated this fasting-induced increase in dopamine level only in KKAy mice. Dopamine receptor D1, D2 expression in the substantia nigra were markedly lower in KKAy mice compared with C57BL/6 mice, while administration of C21 increased their expression in KKAy mice. Conclusions: Our study suggests that AT2 receptor stimulation may be a new therapeutic approach to improve eating disorder associated with dopamine resistance.

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New therapeutic pathways in the RAS

Cited by 35 publications

References 22 publications

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

Activation of angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis attenuates the cardiac reactivity to acute emotional stress

Angiotensin II type 2 receptor signaling affects dopamine levels in the brain and prevents binge eating disorder

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