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

Abstract

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.

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

“…Group I: WKY + PVN vehicle; Group II: WKY + PVN luteolin; Group III: SHRs + PVN vehicle; Group IV: SHRs + PVN luteolin; luteolin (>98% purity) was obtained from Sigma-Aldrich (Saint Louis, MO, USA). Vehicle (artificial cerebrospinal fluid, aCSF) or luteolin (20 µg/0.11 µL, volume: 0.11 µL/h) was injected into the bilateral PVN of rats for 28 days [ 10 , 19 ]. Blood and PVN tissue of all rats were collected for subsequent molecular experiments.…”

“…IL-1β (1:200 dilution, ab-9722, Abcam, Cambridge, UK) and p-PIKKβ (1:50 dilution, sc-21661, Santa Cruz, CA, USA). The specific method is the same as that described previously [ 10 ].…”

“…In the PVN, neuroinflammation, and generation of reactive oxygen species (ROS) increase sympathetic activity in hypertension [ 8 ]. Neuroinflammation as estimated by proinflammatory cytokine level, activation nuclear factor κB (NF-κB), and ROS due to the intensification of oxidative stress reaction were higher and superoxide dismutase (SOD) expression within PVN was lower in various models of hypertensive rats [ 9 , 10 ]. Studies have shown that NF-κB is implicated in the regulation of a variety of inflammatory cell responses, and has been used for the targeted treatment of many inflammatory diseases.…”

Research Progress on the Correlation Between Hypertension and Gut Microbiota

“… 87 , 88 Experiments involving FMT have confirmed the stimulatory effect of the gut microbiota on the sympathetic drive. 89–91 Simultaneously, reducing sympathetic activity is crucial for alleviating structural changes in the cardiovascular system and mitigating hypertension. 92 , 93

Figure 2 Interaction between sympathetic activation and the gut-brain axis.

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Protective effect of resveratrol on mitochondrial biogenesis during hyperoxia-induced brain injury in neonatal pups

“…[21] Because of its ability to cross the blood-brain barrier and play a role in neurons and glial cells, Res and its related polyphenols have been studied in a variety of nervous system disease models. For example, Res can regulate ROS and neurotransmitters in the hypothalamic paraventricular nucleus to reduce sympathetic activity and blood pressure, [22] inhibit the electrophysiological activity of acid ion channels in pain neurons to reduce peripheral pain, [23] and reverse the learning and memory impairment of neonatal rats caused by the inhaled anaesthetic sevoflurane. [24] Res and its derivatives have fewer clinical applications in nervous system diseases and more applications in mild coronaviruses, such as COVID-19; type 2 diabetes nonalcoholic fatty liver disease; and other diseases.…”