Paraventricular Nucleus Infusion of Oligomeric Proantho Cyanidins Improves Renovascular Hypertension

Abstract

Oxidative stress plays an important role in the pathogenesis of hypertension. Oligomeric proantho cyanidins (OPC) is the main polyphenol presents in grape seed and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that OPC can attenuate oxidative stress in the paraventricular nucleus of hypothalamus (PVN), ameliorate neurotransmitter imbalance, decrease the blood pressure and sympathetic activity in renovascular hypertensive rats. After induction of renovascular hypertension by the two-kidney one-clip (2K-1C) method, male Sprague-Dawley rats received chronic bilateral PVN infusion of OPC (20 μg/h) or vehicle via osmotic minipump for 4 weeks. We found that hypertension induced by 2K-1C was associated with the production of reactive oxygen species (ROS) in the PVN. Infusion of OPC in the PVN significantly reduced the systolic blood pressure and norepinephrine in plasma of 2K-1C rats. In addition, PVN infusion of OPC decreased the level of ROS and the expression of stress-related nicotinamide adenine dinucleotide phosphate (NADPH) oxidases subunit NOX4, increased the levels of nuclear factor E2-related factor 2 (Nrf2) and antioxidant enzyme, balanced the content of cytokines, increased expression of glutamic acid decarboxylase and decreased the expression of tyrosine hydroxylase in the PVN of 2K-1C rats. Our findings provided strong evidence that PVN infusion of OPC inhibited the progression of renovascular hypertension through its potent anti-oxidative and anti-inflammatory function in the PVN.

Effects of Nrf1 in Hypothalamic Paraventricular Nucleus on Regulating the Blood Pressure During Hypertension

“…In this experiment, two kidneys and one clip (2K1C) method was used to construct a hypertensive rat model as mentioned before ( Yu et al, 2021 ). Before the experiment, SD male rats were adaptively fed for 1 week, and blood pressure was tested.…”

“…The systolic blood pressure (SBP) was detected using tail-cuff method every week as previously described ( Yu et al, 2021 ). Un-anesthetized rats were warmed to an ambient temperature of 32°C by placing rats in a holding device mounted on a thermostatically controlled warming plate.…”

“…The PVN tissue was homogenized in lysis buffer and Western blotting was performed as previously described ( Yu et al, 2021 ). The protein concentration was measured and loaded onto an SDS-PAGE gel and then transferred to a polyvinylidene fluoride membrane.…”

Exercise Training Attenuates Hypertension via Suppressing ROS/MAPK/NF-κB/AT-1R Pathway in the Hypothalamic Paraventricular Nucleus

“…Previous studies have reported reactive oxygen species (ROS) production in the PVN, which induces abnormal sympathetic activity in the hypertensive rats [ 20 , 21 ]. ROS within the PVN was shown to play important roles in regulating RSNA in the ANG II or high salt-induced hypertension animal models [ 22 , 23 ].…”

Hypothalamic paraventricular nucleus hydrogen sulfide exerts antihypertensive effects in spontaneously hypertensive rats by attenuating oxidative stress via the Nrf2 pathway

“…The hypothalamic paraventricular nucleus (PVN) regulates respiration, blood pressure (BP), and cardiovascular activity as an integrative element of the neuroendocrine and autonomic nervous systems (Rostami & Hatam, 2022;Xia et al, 2021;Yu et al, 2022). We and other research teams have previously demonstrated that reactive oxygen species (ROS) buildup and an unbalanced ratio of anti-to pro-in ammatory cytokines (PICs) in the PVN were shown to be associated with high blood pressure in hypertensive rats (Gao et al, 2021;Kang et al, 2019;Yu et al, 2021). The elevated sympathetic nervous system excitability may be signi cantly in uenced by high ROS and PICs levels in the PVN.…”