Mineralocorticoid and angiotensin II type 1 receptors in the subfornical organ mediate angiotensin II – induced hypothalamic reactive oxygen species and hypertension

Wang, Hongwei; Huang, Bing; White, Roselyn; Chen, Aidong; Ahmad, Monir; Leenen, Frans H. H.

doi:10.1016/j.neuroscience.2016.04.050

Cited by 49 publications

(42 citation statements)

References 34 publications

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“…SFO silencing of a Nox subunit, p22 phox , also attenuated hypertension and vascular inflammation in response to systemic ANG II infusion for 2 wk (606). Interestingly, SFO-specific delivery of an siRNA targeting the mineralocorticoid receptor prevented brain ROS production and the hypertension caused by systemic ANG II infusion in Wistar rats (1106).…”

Section: Sfo Regulation Of Fluid and Sodium Intake And Blood Pressurementioning

confidence: 93%

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

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

821

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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Section: Sfo Regulation Of Fluid and Sodium Intake And Blood Pressurementioning

confidence: 93%

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

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

821

780

View full text Add to dashboard Cite

show abstract

“…DHE Staining. Dihydroethidium (DHE) staining was performed as previously described [40]. Briefly, 10 μm thick frozen brain sections were incubated with 2 μmol/l fluorescent dye DHE (D1168, Thermo Fisher Scientific, Waltham, MA, USA) at 37°C for 30 min in a humidified chamber and protected from light.…”

Section: Neurobehavioral Function Assessmentmentioning

confidence: 99%

Ezetimibe Attenuates Oxidative Stress and Neuroinflammation via the AMPK/Nrf2/TXNIP Pathway after MCAO in Rats

Wang

Matei

et al. 2020

Oxidative Medicine and Cellular Longevity

122

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Oxidative stress and neuroinflammation play essential roles in ischemic stroke-induced brain injury. Previous studies have reported that Ezetimibe (Eze) exerts antioxidative stress and anti-inflammatory properties in hepatocytes. In the present study, we investigated the effects of Eze on oxidative stress and neuroinflammation in a rat middle cerebral artery occlusion (MCAO) model. One hundred and ninety-eight male Sprague-Dawley rats were used. Animals assigned to MCAO were given either Eze or its control. To explore the downstream signaling of Eze, the following interventions were given: AMPK inhibitor dorsomorphin and nuclear factor erythroid 2-related factor 2 (Nrf2) siRNA. Intranasal administration of Eze, 1 h post-MCAO, further increased the endogenous p-AMPK expression, reducing brain infarction, neurologic deficits, neutrophil infiltration, microglia/macrophage activation, number of dihydroethidium- (DHE-) positive cells, and malonaldehyde (MDA) levels. Specifically, treatment with Eze increased the expression of p-AMPK, Nrf2, and HO-1; Romo-1, thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), Cleaved Caspase-1, and IL-1β were reduced. Dorsomorphin and Nrf2 siRNA reversed the protective effects of Eze. In summary, Eze decreases oxidative stress and subsequent neuroinflammation via activation of the AMPK/Nrf2/TXNIP pathway after MCAO in rats. Therefore, Eze may be a potential therapeutic approach for ischemic stroke patients.

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“…In addition, Ang II via the AT1R and a-adrenoreceptors in the SON has been shown to increase vasopressin release (Qadri et al, 1993). The dependence of Ang II on the mineralocoticoid receptor in mediating oxidative stress in the SFO has also been demonstrated (Wang et al, 2015). The effects of Ang II on other neurotransmitters and neuromodulators are mentioned in a subsequent section.…”

Section: Brain Ras and Blood Pressure Controlmentioning

confidence: 93%

Molecular Basis of the Brain Renin Angiotensin System in Cardiovascular and Neurologic Disorders: Uncovering a Key Role for the Astroglial Angiotensin Type 1 Receptor AT1R

Haspula

Clark

2018

J Pharmacol Exp Ther

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The central renin angiotensin system (RAS) is one of the most widely investigated cardiovascular systems in the brain. It is implicated in a myriad of cardiovascular diseases. However, studies from the last decade have identified its involvement in several neurologic abnormalities. Understanding the molecular functionality of the various RAS components can thus provide considerable insight into the phenotypic differences and mechanistic drivers of not just cardiovascular but also neurologic disorders. Since activation of one of its primary receptors, the angiotensin type 1 receptor (AT1R), results in an augmentation of oxidative stress and inflammatory cytokines, it becomes essential to investigate not just neuronal RAS but glial RAS as well. Glial cells are key homeostatic regulators in the brain and are critical players in the resolution of overt oxidative stress and neuroinflammation. Designing better and effective therapeutic strategies that target the brain RAS could well hinge on understanding the molecular basis of both neuronal and glial RAS. This review provides a comprehensive overview of the major studies that have investigated the mechanisms and regulation of the brain RAS, and it also provides insight into the potential role of glial AT1Rs in the pathophysiology of cardiovascular and neurologic disorders.

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Mineralocorticoid and angiotensin II type 1 receptors in the subfornical organ mediate angiotensin II – induced hypothalamic reactive oxygen species and hypertension

Cited by 49 publications

References 34 publications

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

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

Ezetimibe Attenuates Oxidative Stress and Neuroinflammation via the AMPK/Nrf2/TXNIP Pathway after MCAO in Rats

Molecular Basis of the Brain Renin Angiotensin System in Cardiovascular and Neurologic Disorders: Uncovering a Key Role for the Astroglial Angiotensin Type 1 Receptor AT1R

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