TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension

Li, Hong-Bao; Li, Xiang; Huo, Chan-Juan; Su, Qing; Guo, Jing; Yuan, Zuyi; Zhu, Guo‐Qing; Shi, Xiao-Lian; Liu, Jinjun; Kang, Yu-Ming

doi:10.1016/j.taap.2016.06.014

Cited by 52 publications

(46 citation statements)

References 38 publications

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“…Nuclear factor-kappa B (NF-κB) is one of the most important downstream transcription factors responsible for the transcription of PIC, and thereby regulates BP [20,21]. It has been demonstrated that increased PIC activate NF-κB signaling pathway and activation of NF-κB in turn further upregulates PIC [20].…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical labeling was performed in floating sections (18 μm) as previously described [21,22] to identify Fra-like (Fra-LI, a marker of chronic neuronal activation), tumour necrosis factor-alpha (TNF-α) and 67-kDa isoform of glutamate decarboxylase (GAD67) (Santa Cruz Biotechnology, Santa Cruz, California) expressions. Superoxide generation was determined by fluorescent-labelled dihydroethidium (DHE, Molecular Probes) staining as previously described [22,28].…”

Section: Immunohistochemistry and Immunofluorescence Studiesmentioning

confidence: 99%

“…The NF-κB p65 active ELISA (Active Motif, USA) kit was used to measure the binding activity of free NF-κB p65 in nuclear extracts, as described previously [21,31].…”

Section: Elisa Studiesmentioning

confidence: 99%

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

Huo

et al. 2018

Cell Physiol Biochem

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistry and Immunofluorescence Studiesmentioning

confidence: 99%

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

Huo

et al. 2018

Cell Physiol Biochem

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“…The anti-inflammatory effect of TELM has been demonstrated in the literature in other experimental models (Czechowska et al, 2016; Li et al, 2016). …”

Section: Discussionmentioning

confidence: 74%

Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters

et al. 2018

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Oral mucositis (OM) is a common adverse effect resulting from cancer therapy. The OM it has implications that may compromise oncologic treatment and decrease the patient’s quality of life. The therapeutic options to prevent or treat the symptoms of OM are scarce; there is no effective therapy that improves the symptoms. Based on the need for further research for the treatment of OM, the present study objective was to evaluate the effect of telmisartan (TELM) on the OM induced by 5-fluorouracil (5-FU), using as animal model Golden Syrian hamsters. 5-FU followed by mechanical trauma on day 4 was used to induce OM in hamsters. Euthanasia occurred on the day 10. The experiments were constituted by the groups saline, mechanical trauma, 5-FU, and TELM in three doses (1, 5, or 10 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The samples also were used for analysis enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reactions (qPCR). TELM (5 or 10 mg/kg) was able to reduce the inflammatory ulceration and infiltration in the oral mucosa of the animals, decreasing the levels of the cytokines TNF-α and IL-1β. These treatments was minimize the immunostaining for cyclooxygenase-2, matrix metalloproteinase-9, transforming growth factor-β, and smad 2/3. The nuclear transcription factor kappa B (NFκB) p65 and inducible nitric oxide synthase were reduced in the oral mucosa. Finally, TELM (10 mg/kg) increased the PPARγ gene expression and reduced STAT1 and NFκB p65 gene expression relative to the 5-FU group. Therefore, TELM prevents the OM produced by 5-FU on animal model.

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“…Previous studies showed that PPARG plays an important role in adipose differentiation and in susceptibility to type 2 diabetes [7]. In recent years, decreased PPARG levels have been reported in subjects with high blood pressure not only in vitro but also in vivo [8]. …”

Section: Introductionmentioning

confidence: 99%

Associations between PPARG polymorphisms and the risk of essential hypertension

Cai¹,

Zhang²,

Weng³

et al. 2017

PLoS ONE

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BackgroundPeroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the pathogenesis and maintenance of essential hypertension (EH). It has been suggested that polymorphisms of PPARG are associated with the risk of EH. However, findings to date remain controversial. To elucidate the associations between the PPARG Pro12Ala and C161T polymorphisms and EH risk, a meta-analysis was carried out.MethodsA comprehensive literature search of PubMed, Embase, CNKI (Chinese National Knowledge Infrastructure), VIP and Wanfang databases was conducted. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated to estimate the size of the effect using the random-effects model. At the same time, the pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of the PPARG Pro12Ala polymorphism and blood pressure.ResultsFinally, Fifteen papers (seventeen studies) including 4,151 cases and 4,997 controls to evaluate the association of the PPARGPro12Ala polymorphism and EH risk, were included in this study. Overall, the results suggested that Ala allele was associated with the decreased EH risk (for allelic model, OR = 0.757, 95%CI: 0.624–0.918, P = 0.005; for dominant model, OR = 0.771, 95%CI: 0.627–0.946, P = 0.013). The subgroup analysis stratified by ethnicity showed that the significant association between the PPARG Pro12Ala polymorphism and EH was only detected in the Asian subgroup. There was no difference in blood pressure values between Ala carriers and non-carriers. For the C161T polymorphism, only 5 studies comprising 1,118 cases and 1,357 controls met the inclusion criteria. The overall results showed that the PPARG C161T polymorphism was not associated with the risk of EH. But in the subgroup analysis, we found that the PPARG C161T polymorphism significantly associated with the risk of EH in the Asian subgroup (for allelic model, OR = 0.719, 95% CI: 0.537–0.963, P = 0.027; for dominant model, OR = 0.653, 95% CI: 0.439–0.972, P = 0.036).ConclusionOur meta-analysis suggested that the PPARG polymorphisms might be associated with the risk of EH.

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TLR4/MyD88/NF-κB signaling and PPAR-γ within the paraventricular nucleus are involved in the effects of telmisartan in hypertension

Cited by 52 publications

References 38 publications

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

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

Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters

Associations between PPARG polymorphisms and the risk of essential hypertension

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