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

Jhana O. Hendrickx, Sofie De Moudt, Elke Calus, Peter Paul De Deyn, Debby Van Dam, Guido R.Y. De Meyer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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−/−, 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.

Original languageEnglish
Article number1905
Number of pages12
Issue number12
Publication statusPublished - 14-Dec-2021


  • Arterial stiffness
  • Cognitive decline
  • Nitric oxide synthase

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