Chronic perfusion of angiotensin II causes cognitive dysfunctions and anxiety in mice

Duchemin, Sonia; Bélanger, Élisabeth; Wu, Rong; Ferland, Guylaine; Girouard, Hélène

doi:10.1016/j.physbeh.2012.10.005

Cited by 56 publications

(41 citation statements)

References 34 publications

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“…It is therefore possible that microglia in the presence of Ang II undergo phenotypic changes that lead to inflammation, synaptic pruning, and ultimately cognitive impairments. Indeed, these specific changes in the hippocampus are in line with our earlier findings that pressive Ang II leads to cognitive dysfunctions in tasks that are dependent on this region [22]. They are also consistent with a recent study examining the impact of Ang II (1000 ng/kg/min, 28 days perfusion) on synaptic plasticity in mice, showing that systemic Ang II leads to reductions in hippocampal long-term potentiation, decreased density of hippocampal synapses, and reduced expression of key genes involved in synaptic plasticity, such as Bdnf and Homer1 [47].…”

Section: Discussionsupporting

confidence: 91%

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Differential effect of angiotensin II and blood pressure on hippocampal inflammation in mice

Iulita

Vallerand

Beauvillier

et al. 2018

J Neuroinflammation

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Background: Angiotensin II (Ang II), a peptide hormone involved in the development of hypertension, causes systemic and cerebral inflammation, affecting brain regions important for blood pressure control. The cause-andeffect relationship between hypertension and inflammation is two-way, but the role of blood pressure in the induction of cerebral inflammation is less clear. The vulnerability of specific brain regions, particularly those important for memory, is also of interest. Methods: We used molecular biology approaches, immunohistochemistry, and electron microscopy to examine the interdependence between the hypertensive and pro-inflammatory effects of Ang II. We examined the effect of blood pressure by administering a subpressive (200 ng/kg/min) or a pressive Ang II dose (1000 or 1900 ng/kg/min) with and without hydralazine (150 mg/L) for 1 week and used phenylephrine to increase blood pressure independently of the renin-angiotensin system.

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Section: Discussionsupporting

confidence: 91%

“…Alzet osmotic minipumps (model 1007D, Durect Corporation, Cupertino, USA) were subcutaneously implanted as previously described [22]. Mice received bupivacaine hydrochloride (Marcaine, CDMV, Canada, 2 mg/kg s.c.) at the site of the incision before and after minipump implantation.…”

Section: Osmotic Minipump Implantation and Hydralazine Treatmentmentioning

confidence: 99%

Differential effect of angiotensin II and blood pressure on hippocampal inflammation in mice

Iulita

Vallerand

Beauvillier

et al. 2018

J Neuroinflammation

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“…In this study, we elected to use middle-aged BPH/2J mice, a model of spontaneous lifelong hypertension resulting in well-documented and reproducible cognitive deficits (38). We did not assess cognitive function in ANGII-treated mice because higher concentrations of ANGII and longer exposures are needed to observe cognitive deficits (4 weeks) (39,40). Such longer administration times are not compatible with the time course of PVM depletion by CLOD, since PVMs begin to repopulate the perivascular space at this time (27).…”

Section: Nox2 Deletion In Bm Cells (Nox2 -/-mentioning

confidence: 99%

Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension

Faraco¹,

Sugiyama²,

Lane³

et al. 2016

Journal of Clinical Investigation

280

358

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In this study we investigated the contribution of PVMs to the neurovascular and cognitive dysfunction induced by hypertension. We found that depletion of PVMs in models of chronic hypertension suppresses vascular oxidative stress and ameliorates the attendant impairment in neurovascular coupling and endothelium-dependent responses. Studies in bone marrow (BM) chimeras provided evidence that the dysfunction is mediated by ANGII acting on PVM AT1Rs resulting in NOX2-dependent ROS production. Importantly, concomitant to the neurovascular improvement, PVM depletion also rescued cognitive dysfunction. The findings unveil a previously unrecognized role of PVMs in the neurovascular and cognitive dysfunction induced by hypertension, and identify PVMs as a novel pathogenic component of the NVU of critical importance for brain health.

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“…7,8 Furthermore, evidence from pharmacological studies suggests the dual role of RAAS in modulating stress and associated anxiety in different models of stress. [9][10][11] These effects have been mainly attributed to differential changes in AT 1 and AT 2 receptor expression in the stress-responsive brain areas, both inside and outside the blood-brain barrier. [12][13][14] The AT 1 and AT 2 receptor subtypes are widely distributed in different brain areas, including the key areas controlling nociception, such as the anterior cingulated cortex (ACC), prefrontal cortex (PFC), thalamus, periaqueductal gray matter (PAG), amygdala, nucleus accumbens and spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Renin–angiotensin system in pain: Existing in a double life?

Bali

Singh

Jaggi

2014

J Renin Angiotensin Aldosterone Syst

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Apart from the well-documented role of the renin-angiotensin-aldosterone system (RAAS) in regulating the blood pressure and other related parameters, its role in modulating different physiological/pathological functions, including pain, has also been described. Like its dual role in regulating stress-related anxiety and cognitive functions, its dual role has also been documented in pain modulation in different disease states. Drugs blocking the RAAS activation, viz., renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, AT 1 receptor antagonists and aldosterone antagonists, have been shown to produce beneficial effects in migraine and neuropathic and nociceptive pain. Their beneficial effects have been mainly attributed to inhibition of the inflammatory cascade of reactions by inhibiting the generation of key cytokines, including tumor necrosis factor (TNF)-α. On the contrary, clinical as well as preclinical studies have also shown the paininducing actions of renin-angiotensin system (RAS) blocking drugs. Furthermore, the pain-relieving actions of angiotensin II (AngII) and pain-inducing actions of AT 1 blockers have also been described. The pain-inducing actions of ACE inhibitors have been mainly attributed to interference with metabolism of bradykinin and substance P, while the analgesic actions of AngII have been mainly related to activation of brain localized AT 2 receptors and release of endogenous opioids. The present review describes the dual role of the RAAS in different states of pain.

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Chronic perfusion of angiotensin II causes cognitive dysfunctions and anxiety in mice

Cited by 56 publications

References 34 publications

Differential effect of angiotensin II and blood pressure on hippocampal inflammation in mice

Differential effect of angiotensin II and blood pressure on hippocampal inflammation in mice

Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension

Renin–angiotensin system in pain: Existing in a double life?

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