Nrf1 Knock-Down in the Hypothalamic Paraventricular Nucleus Alleviates Hypertension Through Intervention of Superoxide Production-Removal Balance and Mitochondrial Function

Li, Ying; Yu, Xiao-Jing; Xiao, Tong; Chi, Hongli; Zhu, Guo‐Qing; Kang, Yu-Ming

doi:10.1007/s12012-021-09641-6

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…Furthermore, inhibition of ROS with SOD mimics drug, or genetic deletion of a component of the signaling cascade, usually attenuated or delayed the onset of hypertension and preserved the kidney structure and the function 19 . By knocking down nuclear respiratory factor-1 (Nrf1), the superoxide production was further reduced, which relieved hypertension and reduced the target organ damage 20 . The rats without the SOD gene knockout produced considerably less goal-ole ROS than the SOD gene knockout rats as the pressure of renal arteriole perfusion increased 21 .…”

Section: Discussionmentioning

confidence: 99%

Superoxide dismutase as a protective factor for microalbuminuria in hypertensive patients

Wen

et al. 2022

Sci Rep

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Oxidative stress had been linked to hypertensive renal impairment in previous investigations. Superoxide dismutase (SOD) was a clinically available oxidative stress biomarker. The association between SOD and the microalbuminuria in hypertensive patients has not been established. From January 2017 to December 2018, data on 690 patients with essential hypertension were collected retrospectively at Shandong Provincial Qianfoshan Hospital. Patients were divided into hypertension with microalbuminuria group (HM) and hypertension without microalbuminuria group (NHM). Clinical data from patients were collected and compared between the two groups. Spearman correlation analysis was used to analyze the correlation between UACR and SOD. Univariate and multivariate logistic regression analyses were used to screen for the risk factors for HM. Our research included 556 patients in the NHM group and 134 patients in the HM group. Spearman correlation analysis showed a negative correlation between SOD and UACR (P < 0.001). Multivariate logistic regression analysis showed SOD was an independent protective factor in hypertensive patients with HM. In hypertensive patients, a substantial, negative correlation between SOD and early renal damage was found, suggesting that SOD may protect renal function.

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Section: Discussionmentioning

confidence: 99%

Superoxide dismutase as a protective factor for microalbuminuria in hypertensive patients

Wen

et al. 2022

Sci Rep

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“…The method has been described previously [ 34 ]. PI3K, phosphorylated PI3K, Akt, and phosphorylated Akt in the PVN were measured with Western blotting.…”

Section: Methodsmentioning

confidence: 99%

Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus

Gao

Feng

et al. 2023

Nutrients

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Background: Luteolin is widely distributed among a number of vegetal species worldwide. The pharmacological effects of luteolin are diverse and amongst antioxidant, free radical scavenging, and anti-inflammatory activities. Preliminary study showed that luteolin can ameliorate hypertension. However, the precise mechanism needs further investigation. There is no evidence that luteolin affects the paraventricular nucleus of the hypothalamus (PVN), a brain nucleus associated with a critical neural regulator of blood pressure. Our main aim was to explore the effect of luteolin on the PI3K/Akt/NF-κB signaling pathway within the PVN of hypertensive rats. Methods: spontaneously hypertensive rats (SHRs) and corresponding normotensive control rats, the Wistar Kyoto (WKY) rats were divided into four groups and subsequently treated for 4 weeks with bilateral PVN injections of either luteolin (20 µg/0.11 µL, volume: 0.11 µL/h) or vehicle (artificial cerebrospinal fluid). Results: luteolin infusion to the PVN significantly decreased some hemodynamic parameters including the mean arterial pressure (MAP), heart rate (HR), circulating plasma norepinephrine (NE) and epinephrine (EPI). Additionally, there was a decrease in the expressions of the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT), levels of reactive oxygen species (ROS), NAD(P)H oxidase subunit (NOX2, NOX4) in the PVN of SHRs. Meanwhile, the expression of inflammatory cytokines and the activity of nuclear factor κB (NF-κB) p65 in the PVN of SHRs were lowered. Furthermore, immunofluorescence results showed that injection of luteolin in the PVN reduced the expression of tyrosine hydroxylase (TH), and increased that of superoxide dismutase (SOD1) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN of SHRs. Conclusion: Our novel findings revealed that luteolin lowered hypertension via inhibiting NF-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN.

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“…In line with previously cited methods [ 37 ], the non-anesthetized rats were placed on a thermostatically controlled heating plate and heated up to an ambient temperature of 36 ℃ for 15 min, and systolic blood pressure (SBP) was recorded by a non-invasive tail-cuff instrument (BP-300, Chengdu Techman Software Co., Ltd., Chengdu, China) every four days. A seven-day pre-training session before the experiment was necessary for all rats to fully adapt to the measurement procedure.…”

Section: Methodsmentioning

confidence: 99%

Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters

Liu

et al. 2022

Nutrients

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Background: The hypothalamic paraventricular nucleus (PVN) is an important nucleus in the brain that plays a key role in regulating sympathetic nerve activity (SNA) and blood pressure. Silent mating-type information regulation 2 homolog-1 (sirtuin1, SIRT1) not only protects cardiovascular function but also reduces inflammation and oxidative stress in the periphery. However, its role in the central regulation of hypertension remains unknown. It is hypothesized that SIRT1 activation by resveratrol may reduce SNA and lower blood pressure through the regulation of intracellular reactive oxygen species (ROS) and neurotransmitters in the PVN. Methods: The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension in male Sprague-Dawley rats. Then, bilaterally injections of vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL) or resveratrol (a SIRT1 agonist, 160 μmol/L, 0.4 μL) into rat PVN were performed for four weeks. Results: PVN SIRT1 expression was lower in the hypertension group than the sham surgery (SHAM) group. Activated SIRT1 within the PVN lowered systolic blood pressure and plasma norepinephrine (NE) levels. It was found that PVN of 2K1C animals injected with resveratrol exhibited increased expression of SIRT1, copper-zinc superoxide dismutase (SOD1), and glutamic acid decarboxylase (GAD67), as well as decreased activity of nuclear factor-kappa B (NF-κB) p65 and NAD(P)H oxidase (NOX), particularly NOX4. Treatment with resveratrol also decreased expression of ROS and tyrosine hydroxylase (TH). Conclusion: Resveratrol within the PVN attenuates hypertension via the SIRT1/NF-κB pathway to decrease ROS and restore the balance of excitatory and inhibitory neurotransmitters.

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Nrf1 Knock-Down in the Hypothalamic Paraventricular Nucleus Alleviates Hypertension Through Intervention of Superoxide Production-Removal Balance and Mitochondrial Function

Cited by 9 publications

References 53 publications

Superoxide dismutase as a protective factor for microalbuminuria in hypertensive patients

Superoxide dismutase as a protective factor for microalbuminuria in hypertensive patients

Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus

Resveratrol in the Hypothalamic Paraventricular Nucleus Attenuates Hypertension by Regulation of ROS and Neurotransmitters

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