The role of the Nox4-derived ROS-mediated RhoA/Rho kinase pathway in rat hypertension induced by chronic intermittent hypoxia

Lu, Wenyue; Kang, Jian; Hu, Ke; Tang, Si; Zhou, Xin; Xu, Liang; Li, Yuanyuan; Yu, Shuiliang

doi:10.1007/s11325-016-1449-2

Cited by 32 publications

(38 citation statements)

References 71 publications

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“…However, a later study did not find any effect on the angiotensin II hypertensive response in Nox4 -deficient mice [118]. A recent report suggests that Nox4 activity could be required for hypertension mediated by chronic intermittent hypoxia, which could be related to the Nox4 increased expression in the kidney [192]. Interestingly, there are in vivo studies showing an implication of renal Nox4 in the development of salt-induced [193] or angiotensin-induced hypertension [194].…”

Section: Therapeutic Opportunitiesmentioning

confidence: 99%

The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis

Prieto-Bermejo

Hernández‐Hernández

2017

Antioxidants

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Eukaryotic cells have to cope with the constant generation of reactive oxygen species (ROS). Although the excessive production of ROS might be deleterious for cell biology, there is a plethora of evidence showing that moderate levels of ROS are important for the control of cell signaling and gene expression. The family of the nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases or Nox) has evolved to produce ROS in response to different signals; therefore, they fulfil a central role in the control of redox signaling. The role of NADPH oxidases in vascular physiology has been a field of intense study over the last two decades. In this review we will briefly analyze how ROS can regulate signaling and gene expression. We will address the implication of NADPH oxidases and redox signaling in angiogenesis, and finally, the therapeutic possibilities derived from this knowledge will be discussed.

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Section: Therapeutic Opportunitiesmentioning

confidence: 99%

The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis

Prieto-Bermejo

Hernández‐Hernández

2017

Antioxidants

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“…2.3 | CIH model and BP monitoring CIH model was established as previously described (Lu et al, 2017).…”

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confidence: 99%

Sensory plasticity of carotid body is correlated with oxidative stress in paraventricular nucleus during chronic intermittent hypoxia

Liu

Zhang

et al. 2019

Journal Cellular Physiology

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Chronic intermittent hypoxia (CIH) is known to induce hypertension, but the mechanism is not well understood. We hypothesized that sensory plasticity of the carotid body (CB) and oxidative stress in the paraventricular nucleus (PVN) are involved in CIH‐induced hypertension. In this study, rats were exposed to CIH for 28 days (intermittent hypoxia of 21% O2 for 60 s and 5% O2 for 30 s, cyclically repeated for 8 hr/day) and then randomly grouped for intracerebroventricular injection of 5‐HT2 receptor antagonist ritanserin, Rho‐associated protein kinase (ROCK) inhibitor Y‐27632, and NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI), respectively. We found that CIH increased blood pressure (BP), elevated carotid sinus nerve (CSN) and renal sympathetic nerve (RSN) activities, oxidative stress, and cell apoptosis in PVN. NOX‐derived reactive oxygen species (ROS) production and cell apoptosis decreased when CIH‐induced activation of 5‐HT/5‐HT2AR/PKC signaling was inhibited by ritanserin. In addition, RhoA expression was downregulated when oxidative stress was attenuated by DPI, while Y‐27632 decreased the expression of endothelin‐1, which is overexpressed in the vascular wall during hypertension. Moreover, treatment with ritanserin, DPI or Y‐27632 attenuated the sensory plasticity and sympathetic hyperactivity as well as CIH‐induced elevation of BP. In conclusion, CIH‐induced activation of 5‐HT/5‐HT2AR/PKC signaling contributes to NOX‐derived oxidative stress in PVN, which may cause sensory plasticity of CB, RSN hyperactivity, and elevated BP.

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Section: Pharmacological Interventions and Their Molecular Aspectsmentioning

confidence: 99%

“…Rho kinase signaling pathway is recommended as a novel target for treatment of PH (Lu et al, ). Rho associated serine threonine protein kinases (Rho, Ras, Rab, and Ran families) are recommended as a novel potential therapeutic target for treatment of PH (Lu et al, ). Rho kinase suppresses myosin phosphatase activity by phosphorylating the myosin binding subunit of enzyme and thus, increase VSMC contraction (Lopez et al, ).…”

Section: Pharmacological Interventions and Their Molecular Aspectsmentioning

confidence: 99%

“…Rho kinase suppresses myosin phosphatase activity by phosphorylating the myosin binding subunit of enzyme and thus, increase VSMC contraction (Lopez et al, ). Rho kinase has supposed to activate various mediators cellular signaling cascade or mediators including monocyte chemoattractant protein‐1 (MCP‐1), plasminogen activator inhibitor‐1, and NADPH oxidase, which finally can cause vascular remodeling (Table ) (Lopez et al, ; Lu et al, ). Inhibition of Rho kinase cause the diminished expression of eNOS and increase inflammatory mediators in PH (Velayati et al, ).…”

Section: Pharmacological Interventions and Their Molecular Aspectsmentioning

confidence: 99%

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Pulmonary hypertension: Molecular aspects of current therapeutic intervention and future direction

Arora

Sachdeva³

et al. 2017

Journal Cellular Physiology

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Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics, and long acting prostacyclin analog, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH. Understanding precise molecular cascade involved in PH can be useful for designing preclinical animal experiments and human clinical trials to evaluate target specific novel therapeutic interventions for the treatment of PH. In this review, we discussed the possible molecular signaling involved in the pathogenesis of PH and detailed account of the current status of medications employed for the treatment of PH. Moreover, the newly identified potential target sites and alternative approaches for treating the PH have been discussed.

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The role of the Nox4-derived ROS-mediated RhoA/Rho kinase pathway in rat hypertension induced by chronic intermittent hypoxia

Abstract: Hypertension can be induced by CIH in SD rats. The CIH-induced elevation of BP is at least partially mediated via the Nox4-induced ROS/RhoA/ROCK pathway.

Cited by 32 publications

References 71 publications

The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis

The Importance of NADPH Oxidases and Redox Signaling in Angiogenesis

Sensory plasticity of carotid body is correlated with oxidative stress in paraventricular nucleus during chronic intermittent hypoxia

Pulmonary hypertension: Molecular aspects of current therapeutic intervention and future direction

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