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

Abstract

Background: Aerobic exercise training (ExT) is beneficial for hypertension, however, its central mechanisms in improving hypertension remain unclear. Since the importance of the up-regulation of angiotensin II type 1 receptor (AT-1R) in the paraventricular nucleus (PVN) of the hypothalamic in sympathoexcitation and hypertension has been shown, we testified the hypothesis that aerobic ExT decreases blood pressure in hypertensive rats by down-regulating the AT-1R through reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/nuclear factors κB (NF-κB) pathway within the PVN. Methods: Forty-eight male Sprague-Dawley (SD) rats were assigned to the following groups: sham operation (SHAM) + kept sedentary (Sed), SHAM + exercise training (ExT), two kidney-one clamp (2K1C) + Sed, and 2K1C + ExT groups. Results: The 2K1C + Sed hypertensive rats showed higher systolic blood pressure (SBP), upregulated ROS, phosphorylated (p-) p44/42 MAPK, p-p38 MAPK, NF-κB p65 activity, and AT-1R expression in the PVN, and increased circulating norepinephrine (NE) than those of SHAM rats. After eight weeks of aerobic ExT, the 2K1C + ExT hypertensive rats showed attenuated NE and SBP levels, suppressed NF-κB p65 activity, and reduced expression of ROS, p-p44/42 MAPK, p-p38 MAPK, and AT-1R in the PVN, relatively to the 2K1C + Sed group. Conclusions: These data are suggestive of beneficial effects of aerobic ExT in decreasing SBP in hypertensive rats, via down-regulating the ROS/MAPK/NF-κB pathway that targets AT-1R in the PVN, and eventually ameliorating 2K1C-induced hypertension.

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

“…In contrast, anti-inflammatory cytokines, IL-10 or minocycline can produce an antihypertensive response [ 45 , 46 ]. Additional studies showed that the NF-κB activity in PVN increases significantly in various hypertensive models [ 47 ]. Inhibition of NF-κB could attenuate the expression levels of NLRP3, and the expression of IL-1β, and reduce oxidative stress in PVN, then improve hypertension [ 48 ].…”

Norepinephrine-Activated p38 MAPK Pathway Mediates Stress-Induced Cytotoxic Edema of Basolateral Amygdala Astrocytes

“…Mitogen-activated protein kinases (MAPKs) are serine/threonine protein kinases that regulate the cell cycle, cell proliferation, inflammation, and many physiological and pathological processes through intracellular signaling [20,21]. Studies [22,23] have shown that the p38 MAPK signaling pathway plays an important role in mediating the biological responses to NE. Other studies have demonstrated the regulation of aquaporins (AQPs) by p38 MAPK pathway activation in cerebral edema.…”

Impact of Particulate Matter Exposure and Aerobic Exercise on Circulating Biomarkers of Oxidative Stress, Antioxidant Status, and Inflammation in Young and Aged Mice

“…Regular exercise can activate nuclear factor kappa-B (NF-κB) pathways and increase the resistance to cellular stress by activating mitogen-activated protein kinases, which in turn increase the activity of various antioxidant enzymes, such as SOD, CAT, GPX, and glutathione reductase (GR). These enzymes reduce the levels of systemic inflammatory factors, such as C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), and promote the expression of anti-inflammatory cytokines [21,22]. Recently, several studies have shown that exercise could reduce the negative effects of PM exposure and the risk of related diseases [23,24].…”