Inhibition of endothelial nitric oxide synthase reverses the effect of exercise on improving cognitive function in hypertensive rats

Inhibition of endothelial nitric oxide synthase reverses the effect of exercise on improving... Hypertension-induced endothelial dysfunction is associated with β-amyloid (Aβ) deposition, a typical pathology of Alzheimer’s disease (AD). Endothelial nitric oxide synthase (eNOS) phosphorylation, impaired by phosphatidylinositol 3-kinase (PI3K)/protein kinase-B(Akt) pathway abnormalities in hypertensive rats, has a critical role in endothelial function. However, it is unknown whether eNOS participates in the hypertension-induced pathology of AD. In this study, we investigated the role of eNOS in Aβ deposition and cognitive function in stroke-prone spontaneously hypertensive (SHRSP) rats. Physical exercise was used as a promoter, and Nω-nitro l-arginine methyl ester (L-NAME) was used as an inhibitor of eNOS to determine the effects of eNOS on SHRSP rats. Compared with Wistar Kyoto (WKY) rats, the hypertensive challenge caused cognitive impairment, decreased eNOS levels and increased amyloid precursor protein (APP), β-secretase, and Aβ levels in the cortex and hippocampus. Sixteen weeks of exercise lowered blood pressure (BP), promoted eNOS expression, ameliorated Alzheimer’s pathology, and improved cognitive function in 29-week-old SHRSP rats. Furthermore, daily treatment with L-NAME reversed the beneficial effects of exercise on SHRSP rats. Exercise also decreased the protein levels of insulin-like growth factor-1 (IGF-1), PI3K, and phospho-Akt (p-Akt, ser473). In addition, long-term exercise increased the expression levels of IGF-1, PI3K, and p-Akt (ser473) in the brains of SHRSP rats. In conclusion, eNOS downregulation contributed to hypertension-induced Alzheimer pathology and cognitive impairment. Long-term exercise initiated in rats at a young age promoted eNOS expression and attenuated vascular-related Alzheimer’s pathology via the IGF-1/PI3K/p-Akt pathway in SHRSP rats. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hypertension Research Springer Journals

Inhibition of endothelial nitric oxide synthase reverses the effect of exercise on improving cognitive function in hypertensive rats

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Publisher
Nature Publishing Group UK
Copyright
Copyright © 2018 by The Japanese Society of Hypertension
Subject
Medicine & Public Health; Medicine/Public Health, general; Internal Medicine; Public Health; Geriatrics/Gerontology; Obstetrics/Perinatology/Midwifery; Health Promotion and Disease Prevention
ISSN
0916-9636
eISSN
1348-4214
D.O.I.
10.1038/s41440-018-0033-5
Publisher site
See Article on Publisher Site

Abstract

Hypertension-induced endothelial dysfunction is associated with β-amyloid (Aβ) deposition, a typical pathology of Alzheimer’s disease (AD). Endothelial nitric oxide synthase (eNOS) phosphorylation, impaired by phosphatidylinositol 3-kinase (PI3K)/protein kinase-B(Akt) pathway abnormalities in hypertensive rats, has a critical role in endothelial function. However, it is unknown whether eNOS participates in the hypertension-induced pathology of AD. In this study, we investigated the role of eNOS in Aβ deposition and cognitive function in stroke-prone spontaneously hypertensive (SHRSP) rats. Physical exercise was used as a promoter, and Nω-nitro l-arginine methyl ester (L-NAME) was used as an inhibitor of eNOS to determine the effects of eNOS on SHRSP rats. Compared with Wistar Kyoto (WKY) rats, the hypertensive challenge caused cognitive impairment, decreased eNOS levels and increased amyloid precursor protein (APP), β-secretase, and Aβ levels in the cortex and hippocampus. Sixteen weeks of exercise lowered blood pressure (BP), promoted eNOS expression, ameliorated Alzheimer’s pathology, and improved cognitive function in 29-week-old SHRSP rats. Furthermore, daily treatment with L-NAME reversed the beneficial effects of exercise on SHRSP rats. Exercise also decreased the protein levels of insulin-like growth factor-1 (IGF-1), PI3K, and phospho-Akt (p-Akt, ser473). In addition, long-term exercise increased the expression levels of IGF-1, PI3K, and p-Akt (ser473) in the brains of SHRSP rats. In conclusion, eNOS downregulation contributed to hypertension-induced Alzheimer pathology and cognitive impairment. Long-term exercise initiated in rats at a young age promoted eNOS expression and attenuated vascular-related Alzheimer’s pathology via the IGF-1/PI3K/p-Akt pathway in SHRSP rats.

Journal

Hypertension ResearchSpringer Journals

Published: Mar 22, 2018

References

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