Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice
Increasing epidemiological and experimental evidence points to a link between arterial stiffness and rapid cognitive decline. However, the underlying mechanism linking the two diseases is still unknown. The importance of nitric oxide synthases in both diseases is well-defined. In this study, we intr...
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MDPI AG
2021-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/12/1905 |
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| author | Jhana O. Hendrickx Sofie De Moudt Elke Calus Peter Paul De Deyn Debby Van Dam Guido R. Y. De Meyer |
| author_facet | Jhana O. Hendrickx Sofie De Moudt Elke Calus Peter Paul De Deyn Debby Van Dam Guido R. Y. De Meyer |
| author_sort | Jhana O. Hendrickx |
| collection | DOAJ |
| description | Increasing epidemiological and experimental evidence points to a link between arterial stiffness and rapid cognitive decline. However, the underlying mechanism linking the two diseases is still unknown. The importance of nitric oxide synthases in both diseases is well-defined. In this study, we introduced arterial stiffness in both genetic (eNOS<sup>−/−</sup>, endothelial nitric oxide synthase knockout) and pharmacological (N(G)-nitro-L-arginine methyl ester (L-NAME) treatment) NO dysfunction models to study their association with cognitive decline. Our findings demonstrate that the non-selective inhibition of NOS activity with L-NAME induces cardiac dysfunction, arterial stiffness, and a decline in hippocampal-dependent learning and memory. This outcome demonstrates the importance of neuronal NOS (nNOS) in both cardiovascular and neurological pathophysiology and its potential contribution in the convergence between arterial stiffness and cognitive decline. |
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| id | doaj.art-7b11ba64286d4409bdbfc8e69b7eb6a9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T04:33:47Z |
| publishDate | 2021-12-01 |
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| series | Biomedicines |
| spelling | doaj.art-7b11ba64286d4409bdbfc8e69b7eb6a92023-11-23T03:57:27ZengMDPI AGBiomedicines2227-90592021-12-01912190510.3390/biomedicines9121905Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 MiceJhana O. Hendrickx0Sofie De Moudt1Elke Calus2Peter Paul De Deyn3Debby Van Dam4Guido R. Y. De Meyer5Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, BelgiumLaboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, BelgiumLaboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, BelgiumLaboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, BelgiumLaboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, BelgiumLaboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, BelgiumIncreasing epidemiological and experimental evidence points to a link between arterial stiffness and rapid cognitive decline. However, the underlying mechanism linking the two diseases is still unknown. The importance of nitric oxide synthases in both diseases is well-defined. In this study, we introduced arterial stiffness in both genetic (eNOS<sup>−/−</sup>, endothelial nitric oxide synthase knockout) and pharmacological (N(G)-nitro-L-arginine methyl ester (L-NAME) treatment) NO dysfunction models to study their association with cognitive decline. Our findings demonstrate that the non-selective inhibition of NOS activity with L-NAME induces cardiac dysfunction, arterial stiffness, and a decline in hippocampal-dependent learning and memory. This outcome demonstrates the importance of neuronal NOS (nNOS) in both cardiovascular and neurological pathophysiology and its potential contribution in the convergence between arterial stiffness and cognitive decline.https://www.mdpi.com/2227-9059/9/12/1905arterial stiffnesscognitive declinenitric oxide synthase |
| spellingShingle | Jhana O. Hendrickx Sofie De Moudt Elke Calus Peter Paul De Deyn Debby Van Dam Guido R. Y. De Meyer Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice Biomedicines arterial stiffness cognitive decline nitric oxide synthase |
| title | Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice |
| title_full | Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice |
| title_fullStr | Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice |
| title_full_unstemmed | Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice |
| title_short | Long-Term Pharmacological Inhibition of the Activity of All NOS Isoforms Rather Than Genetic Knock-Out of Endothelial NOS Leads to Impaired Spatial Learning and Memory in C57BL/6 Mice |
| title_sort | long term pharmacological inhibition of the activity of all nos isoforms rather than genetic knock out of endothelial nos leads to impaired spatial learning and memory in c57bl 6 mice |
| topic | arterial stiffness cognitive decline nitric oxide synthase |
| url | https://www.mdpi.com/2227-9059/9/12/1905 |
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