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Associations of Angiotensin Converting Enzyme-1 and Angiotensin II Blood Levels and Cognitive Function.

ABSTRACT: BACKGROUND:Emerging evidence suggests a possible role of the renin angiotensin system in the pathophysiologic process of Alzheimer's disease, of which angiotensin converting enzyme-1 (ACE-1) and angiotensin II (ANGII) are important proteins. Few studies evaluated associations between blood ACE-1 and none between ANGII levels, and cognition. OBJECTIVE:Our pilot study was aimed to examine associations between blood ACE-1 and ANG II levels and cognitive function in non-demented participants at baseline and over a 1-year period. METHODS:56 participants were included from the Brain Health Substudy of the Baltimore Experience Corps Study. Linear regression analysis, adjusting for confounders, was used to determine associations between baseline ACE-1 and ANGII, and baseline and 1-year follow-up measures of psychomotor and processing speed, executive function, verbal learning memory and working memory, and whether these associations were mediated by blood pressure. RESULTS:Participants were predominantly female (75%), African-American (93%), with mean age of 67.8 years and education of 14.3 years. There were no associations between baseline ACE-1 or ANGII levels and cognitive function; however, there were significant association between baseline ACE-1 levels and 1-year follow-up Trail Making Test, Part A (?=?0.003, p?=?0.04) and Digit Span (?=?-0.001, p?=?0.02). CONCLUSIONS:In this cognitively intact sample, elevated ACE-1 levels were associated with worse processing speed and working memory after 1 year. Findings from this pilot study suggest that changes in the RAS are associated with alterations in cognitive function warranting further assessment of the role of RAS in neurodegenerative disorders.

SUBMITTER: Yasar S

PROVIDER: S-EPMC5998658 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Associations of Angiotensin Converting Enzyme-1 and Angiotensin II Blood Levels and Cognitive Function.

Yasar Sevil S Varma Vijay R VR Harris Gregory C GC Carlson Michelle C MC

Journal of Alzheimer's disease : JAD 20180101 2

<h4>Background</h4>Emerging evidence suggests a possible role of the renin angiotensin system in the pathophysiologic process of Alzheimer's disease, of which angiotensin converting enzyme-1 (ACE-1) and angiotensin II (ANGII) are important proteins. Few studies evaluated associations between blood ACE-1 and none between ANGII levels, and cognition.<h4>Objective</h4>Our pilot study was aimed to examine associations between blood ACE-1 and ANG II levels and cognitive function in non-demented parti ...[more]

PMID: 29660936

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Project description:Diminished release and function of endothelium-derived nitric oxide coupled with increases in reactive oxygen species production is critical in endothelial dysfunction. Recent evidences have shown that activation of the protective axis of the renin-angiotensin system composed by angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor promotes many beneficial vascular effects. This has led us to postulate that activation of intrinsic angiotensin-converting enzyme 2 would improve endothelial function by decreasing the reactive oxygen species production. In the present study, we tested 1-[[2-(dimetilamino)etil]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT), a small molecule angiotensin-converting enzyme 2 activator, on endothelial function to validate this hypothesis. In vivo treatment with XNT (1 mg/kg per day for 4 weeks) improved the endothelial function of spontaneously hypertensive rats and of streptozotocin-induced diabetic rats when evaluated through the vasorelaxant responses to acetylcholine/sodium nitroprusside. Acute in vitro incubation with XNT caused endothelial-dependent vasorelaxation in aortic rings of rats. This vasorelaxation effect was attenuated by the Mas antagonist D-pro7-Ang-(1-7), and it was reduced in Mas knockout mice. These effects were associated with reduction in reactive oxygen species production. In addition, Ang II-induced reactive oxygen species production in human aortic endothelial cells was attenuated by preincubation with XNT. These results showed that chronic XNT administration improves the endothelial function of hypertensive and diabetic rat vessels by attenuation of the oxidative stress. Moreover, XNT elicits an endothelial-dependent vasorelaxation response, which was mediated by Mas. Thus, this study indicated that angiotensin-converting enzyme 2 activation promotes beneficial effects on the endothelial function and it is a potential target for treating cardiovascular disease.

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Associations of Angiotensin Converting Enzyme-1 and Angiotensin II Blood Levels and Cognitive Function.

Publications

Associations of Angiotensin Converting Enzyme-1 and Angiotensin II Blood Levels and Cognitive Function.

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