Theobald Drew, Sriramula Srinivas
Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Antioxidants (Basel). 2023 Jan 8;12(1):150. doi: 10.3390/antiox12010150.
Hypertension is associated with increased expression of kinin B1 receptors (B1R) and increased levels of pro-inflammatory cytokines within the neurons. We previously reported that angiotensin II (Ang II) upregulates B1R expression and can induce neuroinflammation and oxidative stress in primary hypothalamic neurons. However, the order in which B1R activation, neuroinflammation, and oxidative stress occur has not yet been studied. Using primary hypothalamic neurons from neonatal mice, we show that tumor necrosis factor (TNF), lipopolysaccharides (LPS), and hydrogen peroxide (HO) can upregulate B1R expression and increase oxidative stress. Furthermore, our study shows that B1R blockade with R715, a specific B1R antagonist, can attenuate these effects. To further confirm our findings, we used a deoxycorticosterone acetate (DOCA)-salt model of hypertension to show that oxidative stress is upregulated in the hypothalamic paraventricular nucleus (PVN) of the brain. Together, these data provide novel evidence that relationship between oxidative stress, neuroinflammation, and B1R upregulation in the brain is bidirectional, and that B1R antagonism may have beneficial effects on neuroinflammation and oxidative stress in various disease pathologies.
高血压与神经元中激肽B1受体（B1R）表达增加以及促炎细胞因子水平升高有关。我们之前报道过，血管紧张素II（Ang II）上调B1R表达，并可在原代下丘脑神经元中诱导神经炎症和氧化应激。然而，B1R激活、神经炎症和氧化应激发生的先后顺序尚未得到研究。利用新生小鼠的原代下丘脑神经元，我们发现肿瘤坏死因子（TNF）、脂多糖（LPS）和过氧化氢（HO）可上调B1R表达并增加氧化应激。此外，我们的研究表明，使用特异性B1R拮抗剂R715阻断B1R可减弱这些作用。为进一步证实我们的发现，我们使用醋酸去氧皮质酮（DOCA）-盐高血压模型，发现大脑下丘脑室旁核（PVN）中的氧化应激上调。总之，这些数据提供了新的证据，表明大脑中氧化应激、神经炎症和B1R上调之间的关系是双向的，并且B1R拮抗作用可能对各种疾病病理中的神经炎症和氧化应激具有有益作用。
