Key result
Chronic NOS inhibition with 0.5 mg/mL L-NAME for 16 weeks increased arterial stiffness and reduced spatiotemporal learning and memory similarly in C57BL/6 and hAPP23+/- mice.
Why the study?
Recent data suggest a link between cardiovascular disease and neurodegeneration, prompting an evaluation of how arterial stiffness induced by long-term nitric oxide synthase inhibition impacts neurobehavioral performance.
Does chronic non-selective NOS inhibition with L-NAME increase arterial stiffness and impair spatiotemporal learning and memory in C57BL/6 and hAPP23+/− mice?
Does chronic non-selective NOS inhibition with L-NAME increase arterial stiffness and impair spatiotemporal learning and memory in C57BL/6 and hAPP23+/− mice?
Chronic NOS inhibition induces arterial stiffness and cognitive impairment regardless of genetic predisposition to Alzheimer's disease, highlighting the role of nNOS in cognitive aging.
Links NOS inhibition to stiffness and memory loss in mice; hypothesis-generating for vascular-cognitive mechanisms, human translation open.
Due to global population growth, age-related disorders like cardiovascular disease and dementia are anticipated to increase. Recent data suggests a connection between cardiovascular disease and neurodegeneration, especially focusing on arterial stiffness (AS) and Alzheimer’s disease (AD). In light of this, we conducted a study to explore the impact of long-term nitric oxide synthase (NOS) isoform inhibition, which leads to AS, on neurobehavioral performance. We also compared these effects in an AD model and control mice. C57BL/6 and hAPP23+/− mice (an established AD model) were given 0.5 mg/mL N(G)-Nitro-L-Arginine Methyl Ester (L-NAME) in their drinking water for 16 weeks. Our findings indicate that chronic non-selective NOS inhibition increased AS and reduced spatiotemporal learning and memory in both C57BL/6 and hAPP23+/− mice. These effects were consistent across both groups, emphasizing the role of neuronal NOS (nNOS) in cognitive aging, regardless of genetic predisposition to AD.
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Hendrickx et al. (2023) studied Alzheimer's disease and arterial stiffness. N(G)-Nitro-L-Arginine Methyl Ester (L-NAME) was evaluated on Arterial stiffness and spatiotemporal learning and memory. Chronic NOS inhibition with 0.5 mg/mL L-NAME for 16 weeks increased arterial stiffness and reduced spatiotemporal learning and memory similarly in C57BL/6 and hAPP23+/- mice.
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