Kinin B1 Receptor Mediates Bidirectional Interaction between Neuroinflammation and Oxidative Stress
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Date
2023-05-02
Access
2025-05-01
Authors
Theobald, Drew
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Publisher
East Carolina University
Abstract
Hypertension is the leading risk factor for cardiovascular disease and affects nearly half the adults in the United States. It is well established that hypertension is a low-grade inflammatory condition and is associated with increased release of proinflammatory cytokines, elevated oxidative stress levels, and increased activity of the kallikrein-kinin system (KKS). The KKS is a family of vasoactive proinflammatory peptides that play a vital role in regulating blood pressure. Activation of kinin B1 receptor (B1R) results in increased inflammation and vasoconstrictive effects which can ultimately lead to hypertension. Previously, we showed that angiotensin II (Ang II) can upregulate B1R expression and can induce oxidative stress and neuroinflammation in primary neurons. However, the order at which this occurs has not yet been investigated. In this study, we aim to determine the relationships between neuroinflammation, oxidative stress, and activation of B1R in both primary hypothalamic neurons and primary hypothalamic microglia. Following stimulation with tumor necrosis factor (TNF), lipopolysaccharide (LPS), or hydrogen peroxide (H2O2), we were able to identify a significant increase in reactive oxygen species production, inflammation, and B1R expression. Furthermore, we showed that B1R blockade using a B1R specific antagonist can attenuate these effects in both neurons and microglia. Together, these data provide novel evidence that the interaction between neuroinflammation, oxidative stress, and B1R activation in the brain is bidirectional and that blocking B1R may serve as a potential therapeutic target for neuroinflammation and oxidative stress in various disease pathologies.