Exercise Training Attenuates Proinflammatory Cytokines, Oxidative Stress and Modulates Neurotransmitters in the Rostral Ventrolateral Medulla of Salt-Induced Hypertensive Rats

Abstract

Background/Aims: Exercise training (ExT) was associated with cardiovascular diseases including hypertension. The rostral ventrolateral medulla (RVLM) is a key region for central control of blood pressure and sympathetic nerve activity. Therefore, this study aimed to investigate the mechanisms within RVLM that can influence exercise training induced effects in salt-induced hypertension. Methods: Male Wistar rats were fed with a normal salt (0.3%) (NS) or a high salt (8%) (HS) diet for 12 weeks to induce hypertension. Then these rats were given moderate-intensity ExT for a period of 12 weeks. RVLM was used to determine glutamate and gamma-aminobutyric acid (HPLC), phosphorylated IKKβ, Fra-LI, 67-kDa isoform of glutamate decarboxylase (GAD67), proinflammatory cytokines (PIC) and NADPH-oxidase (NOX) subunits expression (Immunohistochemistry and Immunofluorescence, Western blotting). PIC and NF-κB p65 activity in the plasma were evaluated by ELISA studies. Renal sympathetic nerve activity (RSNA) was recorded and analyzed using the PowerLab system. Results: High salt diet resulted in increased mean arterial pressure and cardiac hypertrophy. These high salt diet rats had higher RVLM levels of glutamate, PIC, phosphorylated IKKβ, NF-κB p65 activity, Fra-LI, superoxide, NOX-2 (gp91^phox) and 4, and lower RVLM levels of gamma-aminobutyric acid and GAD67, and higher plasma levels of PIC, norepinephrine, and higher RSNA. ExT attenuated these changes in salt-induced hypertensive rats. Conclusions: These findings suggest that high salt diet increases the activity of NF-κB and the levels of PIC and oxidative stress, and induces an imbalance between excitatory and inhibitory neurotransmitters in the RVLM. ExT attenuates hypertension and cardiac hypertrophy partially mediated by attenuating oxidative stress and modulating neurotransmitters in the RVLM.

Melatonin decreases M1 polarization via attenuating mitochondrial oxidative damage depending on UCP2 pathway in prorenin-treated microglia

“…Active oxidase (O 2- ) generates superoxide by transferring reducing equivalents from NADPH or NADH to oxygen. Evidences have indicated that NADPH oxidase is extensively expressed in tissues and is the major source of ROS in oxidative-related hypertension animals[27,28]. Our results implied that NADPH oxidase-mediated prorenin-induced ROS overproduction in microglia.…”

Swimming training improves cardiovascular autonomic dysfunctions and prevents renal damage in rats fed a high‐sodium diet from weaning

“…Swimming exercise training restored the hexamethonium‐induced hypotension of HS rats, which supports the idea that autonomic adaptations to swimming training largely contribute to its anti‐hypertensive effects (Barbosa Neto et al., 2013; Cox et al., 1985; Lemos et al., 2018; Neto et al., 2017). Other studies further corroborate the hypothesis that the reduction in the BP levels due to regular exercise training could be sympathetically mediated since Wistar rats fed 8% NaCl diet and exercise‐trained on a treadmill showed BP restored to the basal levels and attenuation of sympathoexcitation (Li et al., 2018). The influence of the HS diet and ST on autonomic adaptations was further evaluated by variability analysis of cardiac interval and systolic blood pressure.…”

“…Nevertheless, other evidence showed that aerobic treadmill exercise was not effective to reduce the high BP of Dahl‐salt‐sensitive rats under 8% NaCl diet (Ogawa et al., 2020). One of the working hypotheses for the anti‐hypertensive effects of exercise training could be its effectiveness to restore the autonomic balance disfavouring sympathetic tone (de Abreu et al., 2009; Li et al., 2018; Liu et al., 2000). Proposed mechanisms rely on changes in the reflex control of BP, mainly in the baroreflex (Krieger et al., 2001; Niemela et al., 2008; Silva et al., 1997).…”

“…It has been associated with several cardiovascular benefits by inducing physiological adaptations in key systems, such as the neural and renal, that control blood pressure (BP) (Kramer et al, 2002;Peng et al, 2012;Totou et al, 2018). Post-exercise reduction in resting sympathetic activity has been reported in experimental animal models of hypertension (Kramer et al, 2002;Krieger et al, 1999Krieger et al, , 2001Li et al, 2018) as well as in hypertensive subjects (Halliwill, 2001;Pescatello et al, 2015;Rogers et al, 1996). Exercise also prevents the progression of damage in critical organs involved with BP regulation such as kidneys, heart and vasculature through a variety of mechanisms (Barbosa Neto et al, 2013;Melo et al, 2003;Peng et al, 2012;Soares et al, 2011;Totou et al, 2018).…”

Non-invasive vagus nerve stimulation attenuates proinflammatory cytokines and augments antioxidant levels in the brainstem and forebrain regions of Dahl salt sensitive rats

“…The present study explored whether LLTS activated the central antioxidant pathway in order to reduce the HS-induced oxidative stress. Even though oxidative stress was not measured in the present study, it has been well established by numerous other studies using similar animal model 33,36 . The present study found that LLTS significantly upregulated the mRNA of Nrf2 in the SP5 and SFO suggesting that LLTS increases antioxidant capacity at the central level.…”