Cognitive enhancement following acute losartan in normotensive young adults

Mechaeil, Rasha; Gard, Paul R.; Jackson, Anne; Rusted, Jennifer

doi:10.1007/s00213-011-2257-9

Cited by 30 publications

(16 citation statements)

References 61 publications

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“…Excess Ang II was linked to increased blood pressure, decreased cerebrovascular compliance and enhanced brain inflammation, all recognized risk factors for AD, while Ang II type 1 receptor (AT1R) blockade suppressed such processes [6,7]. Moreover, application of AT1R blockers to rodents led to attenuated neurotoxic accumulation and cognitive deficits [8][9][10][11][12]. In our laboratory, central infusion of Ang II significantly promoted Ab production via enhanced amyloidogenic processing [13].…”

Section: Introductionmentioning

confidence: 82%

Central angiotensin II‐induced Alzheimer‐like tau phosphorylation in normal rat brains

et al. 2012

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Edited by Barry HalliwellKeywords: Angiotensin II Glycogen synthase kinase 3b Tau Alzheimer disease a b s t r a c t Growing evidence suggests that Alzheimer disease (AD) origins in vascular lesions. As the crucial mediator of vascular pathology, angiotensin II-induced significant amyloid production in our laboratory, although amyloid neurotoxicity depended on phosphorylated tau (p-tau) in recent studies. In the present study, p-tau levels were significantly elevated by central angiotensin II via glycogen synthase kinase 3b (GSK 3b) and other tau kinases. Moreover, angiotensin II-induced cognitive impairment and tau phosphorylation was attenuated by losartan and a GSK 3b inhibitor. These findings implicate Ang II as a crucial mediator of AD pathology and a link between cardiovascular events and AD.

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Section: Introductionmentioning

confidence: 82%

Central angiotensin II‐induced Alzheimer‐like tau phosphorylation in normal rat brains

et al. 2012

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“…Moreover, enhancing memory effects were observed in humans treated with ARBs. Losartan improved cognitive function, mainly immediate and delayed memory in elderly hypertensive humans (Fogari et al 2003 ) and in healthy young adults (Mechaeil et al 2011 ). Accumulated data unequivocally indicate the beneficial effect of ARBs in memory impairment.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications

et al. 2017

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Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan produced by kynurenine aminotransferase II (KAT II) in the brain. Antagonism towards all ionotropic glutamate (GLU) receptors is the main mechanism of KYNA action. An elevated brain level of KYNA is linked with memory impairment and psychotic symptoms. The aim of this study was to examine the influence of three ARBs: irbesartan, losartan, and telmisartan on KYNA production and KAT II activity in rat brain. The effect of ARBs on KYNA production was analyzed in rat brain cortical slices and on isolated KAT II enzyme. Irbesartan, losartan, and telmisartan decreased KYNA production and KAT II activity in a dose-dependent manner in rat brain cortex in vitro. Molecular docking suggested that the examined ARBs could bind to an active site of KAT II. In conclusion, ARBs decrease KYNA production in rat brain by direct inhibition of KAT II enzymatic activity. This novel mechanism of ARBs action may be advantageous in the treatment of cognitive impairment or the management of schizophrenia.Electronic supplementary materialThe online version of this article (doi:10.1007/s12640-017-9781-2) contains supplementary material, which is available to authorized users.

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“…With regard to the medication issue, recent research suggests that angiotensin II receptor antagonists might both lower blood pressure and improve prospective remembering. Mechaeil, Gard, Jackson, and Rusted (2011) reported that an acute 50mg dose of losartan increased nonfocal prospective memory performance, though this effect was observed in normotensive younger adults. However, in a group of hypertensive older adults, Hajjar et al (2012) found that 12-months of taking 32mg of candesartan controlled blood pressure and improved executive control performance.…”

Section: Discussionmentioning

confidence: 96%

Evidence for a detrimental relationship between hypertension history, prospective memory, and prefrontal cortex white matter in cognitively normal older adults

Scullin

Gordon

Shelton

et al. 2013

Cogn Affect Behav Neurosci

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Hypertension affects many older adults and is associated with impaired neural and cognitive functioning. We investigated whether a history of hypertension was associated with impairments to prospective memory, which refers to the ability to remember to perform delayed intentions such as remembering to take medication. Thirty-two cognitively-normal older adult participants with or without a history of hypertension (self-reported) performed two laboratory prospective memory tasks, one that relies more strongly on executive control (nonfocal prospective memory) and one that relies more strongly on spontaneous memory retrieval processes (focal prospective memory). We observed hypertension-related impairments for nonfocal, but not focal, prospective memory. To complement our behavioral approach, we conducted a retrospective analysis of available structural magnetic resonance imaging data. Lower white matter volume estimates in the anterior prefrontal cortex (aPFC) were associated with lower nonfocal prospective memory and with a history of hypertension. A history of hypertension may be associated with worsened executive control and lower prefrontal white matter volume. The translational implication is that individuals who must remember to take antihypertensive medications and to monitor their blood pressure at home may be impaired in the executive control process that helps to support these prospective memory behaviors.

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Cognitive enhancement following acute losartan in normotensive young adults

Abstract: The findings highlight a cognitive-enhancing potential for losartan on compromised cognitive systems and emphasise the potential of AIIAs to produce benefits over and above hypertension control.

Cited by 30 publications

References 61 publications

Central angiotensin II‐induced Alzheimer‐like tau phosphorylation in normal rat brains

Central angiotensin II‐induced Alzheimer‐like tau phosphorylation in normal rat brains

Angiotensin II Type 1 Receptor Blockers Inhibit KAT II Activity in the Brain—Its Possible Clinical Applications

Evidence for a detrimental relationship between hypertension history, prospective memory, and prefrontal cortex white matter in cognitively normal older adults

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