BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II

Schaich, Christopher L.; Wellman, Theresa L.; Koi, Blanka; Erdös, Benedek

doi:10.1016/j.autneu.2016.02.011

Cited by 20 publications

(24 citation statements)

References 52 publications

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“…Other research groups have reported that candesartan and other potent AT1R blockers successfully attenuated death of dopaminergic neurons induced by the a-synclein. They reported that the blockade of the Ang II/AT1R axis and upregulation of peroxisome proliferator-activated receptor gamma might reduce inflammation by modulating neurotrophic factors (NFs) that activate neuroprotective pathways (Wang et al, 2014;Sathiya et al, 2013;Tong et al, 2016). In addition, telmisartan was found to attenuate lipopolysaccharide induced NO, TNF-a, interleukin 1 beta (IL1-b) as a possible novel neuroprotective mechanism, reinforcing the hypothesis that brain RAS may regulate memory via neuroinflammation (Montgomery et al, 2012, Nakamura andLipton, 2011;Goel et al, 2015).…”

Section: Neuro-inflammationmentioning

confidence: 86%

Role of brain renin angiotensin system in neurodegeneration: An update

Abiodun¹,

Ola²

2020

Saudi Journal of Biological Sciences

110

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a b s t r a c tRenin angiotensin system (RAS) is an endocrine system widely known for its physiological roles in electrolyte homeostasis, body fluid volume regulation and cardiovascular control in peripheral circulation. However, brain RAS is an independent form of RAS expressed locally in the brain, which is known to be involved in brain functions and disorders. There is strong evidence for a major involvement of excessive brain angiotensin converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin type-1 receptor (AT-1R) axis in increased activation of oxidative stress, apoptosis and neuroinflammation causing neurodegeneration in several brain disorders. Numerous studies have demonstrated strong neuroprotective effects by blocking AT1R in these brain disorders. Additionally, the angiotensin converting enzyme 2 (ACE2)/Angiotensin (1-7)/Mas receptor (MASR), is another axis of brain RAS which counteracts the damaging effects of ACE/Ang II/AT1R axis on neurons in the brain. Thus, angiotensin II receptor blockers (ARBs) and activation of ACE2/Angiotensin (1-7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenerative diseases. Here in this review article, we discuss the expression of RAS in the brain and highlight how altered RAS level may cause neurodegeneration. Understanding the pathophysiology of RAS and their links to neurodegeneration has enormous potential to identify potentially effective pharmacological tools to treat neurodegenerative diseases in the brain.

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Section: Neuro-inflammationmentioning

confidence: 86%

Role of brain renin angiotensin system in neurodegeneration: An update

Abiodun¹,

Ola²

2020

Saudi Journal of Biological Sciences

110

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“…Recently Schaich et al (2016) demonstrated that microinjections of BDNF into the PVN result in an acute increase in MAP that are attenuated by prior treatment with the AT1R antagonist losartan in both conscious and anesthetized rats. The authors suggest that there may be interplay between AT1R and TrkB signaling mechanisms in modulating sympathetic neuronal activity.…”

Section: Discussionmentioning

confidence: 99%

“…Neurotrophic factors not only contribute to synaptic connectivity but also mediate changes in neuronal excitability (Benarroch, 2015; Blum et al, 2005; Cao et al, 2010; Rose et al, 2004). To this end, recent studies have investigated the contribution of the ubiquitous neurotrophin brain-derived neurotrophic factor (BDNF) toward promoting autonomic imbalance during RAS activation (Becker et al, 2016; Becker et al, 2015; Clayton et al, 2014; Erdos et al, 2015a; Schaich et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Central TrkB blockade attenuates ICV angiotensin II-hypertension and sympathetic nerve activity in male Sprague-Dawley rats

Becker

Wang

Zucker

2017

Autonomic Neuroscience

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Increased sympathetic nerve activity and the activation of the central renin-angiotensin system are commonly associated with cardiovascular disease states such as hypertension and heart failure, yet the precise mechanisms contributing to the long-term maintenance of this sympatho-excitation are incompletely understood. Due to the established physiological role of neurotrophins contributing towards neuroplasticity and neuronal excitability along with recent evidence linking the renin-angiotensin system and brain-derived neurotrophic factor (BDNF) along with its receptor (TrkB), it is likely the two systems interact to promote sympatho-excitation during cardiovascular disease. However, this interaction has not yet been fully demonstrated, in vivo. Thus, we hypothesized that central angiotensin II (Ang II) treatment will evoke a sympatho-excitatory state mediated through the actions of BDNF/TrkB. We infused Ang II (20 ng/min) into the right lateral ventricle of male Sprague-Dawley rats for twelve days with or without the TrkB receptor antagonist, ANA-12 (50 ng/h). We found that ICV infusion of Ang II increased mean arterial pressure (+40.4 mmHg), increased renal sympathetic nerve activity (+19.4% max activity), and induced baroreflex dysfunction relative to vehicle. Co-infusion of ANA-12 attenuated the increase in blood pressure (−20.6 mmHg) and prevented the increase in renal sympathetic nerve activity (−22.2% max) and baroreflex dysfunction relative to Ang II alone. Ang II increased thirst and decreased food consumption, and Ang II + ANA-12 augmented the thirst response while attenuating the decrease in food consumption. We conclude that TrkB signaling is a mediator of the long-term blood pressure and sympathetic nerve activity responses to central Ang II activity. These findings demonstrate the involvement of neurotrophins such as BDNF in promoting Ang II-induced autonomic dysfunction and further implicate TrkB signaling in modulating presympathetic autonomic neurons during cardiovascular disease.

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“…TrkB blockade decreases the pressor and sympathoexcitatory effects of centrally administered ANG II, suggesting that the BDNF/TrkB pathway is required to mediate ANG II-dependent responses (63). Interestingly, central infusion of an AT 1 R blocker, losartan, or an ACE inhibitor, lisinopril, as well as ganglionic blockade attenuates central BDNF-induced blood pressure elevation (924), further suggesting a feed-forward relationship in brain between the BDNF/TrKB pathway and the RAS.…”

Section: Sympathoexcitatory Actionmentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

783

780

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II

Cited by 20 publications

References 52 publications

Role of brain renin angiotensin system in neurodegeneration: An update

Role of brain renin angiotensin system in neurodegeneration: An update

Central TrkB blockade attenuates ICV angiotensin II-hypertension and sympathetic nerve activity in male Sprague-Dawley rats

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

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