肾素-血管紧张素系统(RAS)的激活引发下丘脑室旁核(PVN)的氧化应激和炎症反应,反过来增加交感神经过度活动,这是高血压的主要原因。吡啶斯的明通过抑制心肌组织的RAS而具有心脏保护作用。然而,吡啶斯的明是否通过抑制PVN的RAS来减轻高血压尚不清楚.因此,我们研究了吡啶斯的明对双肾一夹(2K1C)诱导的高血压的作用和机制。2K1C大鼠接受吡啶斯的明,或者不是,八个星期。心血管功能,血液动力学参数,并测量了自主活动。促炎/抗炎细胞因子的PVN水平,氧化应激,和RAS信号分子进行了评估。我们的结果表明,高血压伴有心血管功能障碍和自主神经失衡,其特征是交感神经增强但迷走神经活动减弱。白细胞介素-6(IL-6)的PVN水平,肿瘤坏死因子-α(TNF-α),活性氧(ROS),NOX-2和丙二醛(MDA)升高;IL-10和超氧化物歧化酶(SOD)降低。此外,RAS信号通路被激活,血管紧张素转换酶(ACE)水平升高,血管紧张素II(AngII),AngⅡ1型受体(AT1R)和AT2R程度降低。吡啶斯的明降低血压,改善心血管功能,与自主平衡的恢复有关。同时,吡啶斯的明降低PVNIL-6,TNF-α,ROS,NOX-2和MDA水平,IL-10和SOD水平升高。此外,吡啶斯的明抑制PVNACE,AngII,AT1R水平和AT2R表达增加。吡啶斯的明通过抑制RAS诱导的PVN氧化应激和炎症来减轻高血压。
Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension.
Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether
pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of
pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension. 2K1C rats received
pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated. Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression.
Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.