Chronic restraint stress increases angiotensin II potency in the rat carotid: role of cyclooxygenases and reactive oxygen species

Côco, Hariane; Pernomian, Laena; Pereira, Priscila Cristina; Gomes, Mayara Santos; Marchi, Kátia Colombo; Lopes, Alexandre H.; Cunha, Thiago M.; Tirapelli, Carlos Renato; Oliveira, Ana Maria de

doi:10.1111/jphp.12659

“…Mental stress can induce NOX activation in the endothelium of thoracic aorta [ 63 ] and increase the expression of NOX-4 in carotid [ 64 , 65 ]. This study shows the NOX activation in the brain vessels and the expression of NOX subunits in mRNA and protein levels upon mental stress.…”

Section: Discussionmentioning

confidence: 99%

Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress

Zhu

¹

,

Haddad

²

,

Yun

³

et al. 2023

Mediators of Inflammation

2

1

0

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Background. Cerebrovascular disease (CVD) is recognized as the leading cause of permanent disability worldwide. Depressive disorders are associated with increased incidence of CVD. The goal of this study was to establish a chronic restraint stress (CRS) model for mice and examine the effect of stress on cerebrovascular inflammation and oxidative stress responses. Methods. A total of forty 6-week-old male C57BL/6J mice were randomly divided into the CRS and control groups. In the CRS group ( n = 20 ), mice were placed in a well-ventilated Plexiglas tube for 6 hours per day for 28 consecutive days. On day 29, open field tests (OFT) and sucrose preference tests (SPT) were performed to assess depressive-like behaviors for the two groups ( n = 10 /group). Macrophage infiltration into the brain tissue upon stress was analyzed by measuring expression of macrophage marker (CD68) with immunofluorescence in both the CRS and control groups ( n = 10 /group). Cerebral microvasculature was isolated from the CRS and controls ( n = 10 /group). mRNA and protein expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and macrophage chemoattractant protein-1 (MCP-1) in the brain vessels were measured by real-time PCR and Western blot ( n = 10 /group). Reactive oxygen species (ROS), hydrogen peroxide (H2O2), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activities were quantified by ELISA to study the oxidative profile of the brain vessels ( n = 10 /group). Additionally, mRNA and protein expressions of NOX subunits (gp91phox, p47phox, p67phox, and p22phox) in the cerebrovascular endothelium were analyzed by real-time PCR and Western blot ( n = 10 /group). Results. CRS decreased the total distances ( p < 0.05 ) and the time spent in the center zone in OFT ( p < 0.001 ) and sucrose preference test ratio in SPT ( p < 0.01 ). Positive ratio of CD68+ was increased with CRS in the entire region of the brain ( p < 0.001 ), reflecting increased macrophage infiltration. CRS increased the expression of inflammatory factors and oxidative stress in the cerebral microvasculature, including TNF-α ( p < 0.001 ), IL-1β ( p < 0.05 ), IL-6 ( p < 0.05 ), VCAM-1 ( p < 0.01 ), MCP-1 ( p < 0.01 ), ROS ( p < 0.001 ), and H2O2 ( p < 0.001 ). NADPH oxidase (NOX) was activated by CRS ( p < 0.01 ), and mRNA and protein expressions of NOX subunits (gp91phox, p47phox, p67phox, and p22phox) in brain microvasculature were found to be increased. Conclusions. To our knowledge, this is the first study to demonstrate that CRS induces depressive stress and causes inflammatory and oxidative stress responses in the brain microvasculature.

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“…The relative isoform selectivity renders this compound a useful tool (when a relatively low concentration of ML171 is employed) to elucidate the contribution of Nox1 to redox-signaling. For example, a recent study on the effects of chronic restraint stress on vascular function showed that ML171 (0.5 μM) reduced AngII-initiated vasoconstriction in rat carotid arteries in the presence and absence of endothelium, implying that Nox1-derived ROS positively influence AngII-mediated contraction in carotid arterial smooth muscle cells [237]. Another study comparing endothelial function of coronary arteries from male and female pigs reported that 100 μM ML171 enhanced bradykinin-induced endothelium-dependent relaxation in male rather than female porcine coronary arteries [238].…”

Section: Nox Inhibitors As Therapeutics For Microvascular Diseasesmentioning

confidence: 99%

Microvascular NADPH oxidase in health and disease

Li

¹

,

Pagano

²

2017

Free Radical Biology and Medicine

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The systemic and cerebral microcirculation contribute critically to regulation of local and global blood flow and perfusion pressure. Microvascular dysfunction, commonly seen in numerous cardiovascular pathologies, is associated with alterations in the oxidative environment including potentiated production of reactive oxygen species (ROS) and subsequent activation of redox signaling pathways. NADPH oxidases (Noxs) are a primary source of ROS in the vascular system and play a central role in cardiovascular health and disease. In this review, we focus on the roles of Noxs in ROS generation in resistance arterioles and capillaries, and summarize their contributions to microvascular physiology and pathophysiology in both systemic and cerebral microcirculation. In light of the accumulating evidence that Noxs are pivotal players in vascular dysfunction of resistance arterioles, selectively targeting Nox isozymes could emerge as a novel and effective therapeutic strategy for preventing and treating microvascular diseases.

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“…Causal involvement of RAAS activity is supported by beneficial effects of ramipril and losartan. Chronic stress may excessively activate the RAAS (544) and increase arterial sensitivity to angiotensin (545). Chronic elevations in angiotensin II also induce inflammation, endothelial dysfunction and senescence (546, 547), while angiotensin receptor antagonism protects against the effects of chronic stress (548).…”

Section: Chronic Stress Modifies Vascular Function and Structure And ...mentioning

confidence: 99%

The sex-dependent response to psychosocial stress and ischaemic heart disease

Helman

¹

,

Headrick

²

,

Stapelberg

³

et al. 2023

Front. Cardiovasc. Med.

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Stress is an important risk factor for modern chronic diseases, with distinct influences in males and females. The sex specificity of the mammalian stress response contributes to the sex-dependent development and impacts of coronary artery disease (CAD). Compared to men, women appear to have greater susceptibility to chronic forms of psychosocial stress, extending beyond an increased incidence of mood disorders to include a 2- to 4-fold higher risk of stress-dependent myocardial infarction in women, and up to 10-fold higher risk of Takotsubo syndrome—a stress-dependent coronary-myocardial disorder most prevalent in post-menopausal women. Sex differences arise at all levels of the stress response: from initial perception of stress to behavioural, cognitive, and affective responses and longer-term disease outcomes. These fundamental differences involve interactions between chromosomal and gonadal determinants, (mal)adaptive epigenetic modulation across the lifespan (particularly in early life), and the extrinsic influences of socio-cultural, economic, and environmental factors. Pre-clinical investigations of biological mechanisms support distinct early life programming and a heightened corticolimbic-noradrenaline-neuroinflammatory reactivity in females vs. males, among implicated determinants of the chronic stress response. Unravelling the intrinsic molecular, cellular and systems biological basis of these differences, and their interactions with external lifestyle/socio-cultural determinants, can guide preventative and therapeutic strategies to better target coronary heart disease in a tailored sex-specific manner.

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Chronic restraint stress increases angiotensin II potency in the rat carotid: role of cyclooxygenases and reactive oxygen species

Abstract: Stress increases AngII potency in rat carotid by a mechanism that involves the increased generation of PGI and H O and the activation of Akt pathway. Such mechanism could play a pathophysiological role in cardiovascular diseases correlated with stress.

Cited by 8 publications

References 60 publications

Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress

Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress

Microvascular NADPH oxidase in health and disease

The sex-dependent response to psychosocial stress and ischaemic heart disease

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