Basic Science and Pathogenesis.

Background: Cerebral microvascular dysfunction and nitro-oxidative stress are present in patients with Alzheimer's disease (AD) and may contribute to disease progression and severity. A pro-nitro-oxidative environment can lead to post-translational modifications of ion channels central to microvascular regulation in the brain, including the large conductance Ca-activated K channels (BK). Nitro-oxidative modulation of BK can resulting in decreased activity and vascular hyper-contractility, thus compromising neurovascular regulation.

Sex-specific mechanisms of cerebral microvascular BK dysfunction in a mouse model of Alzheimer's disease.

Background: Cerebral microvascular dysfunction and nitro-oxidative stress are present in patients with Alzheimer's disease (AD) and may contribute to disease progression and severity. Large conductance Ca -activated K channels (BK ) play an essential role in vasodilatory responses and maintenance of myogenic tone in resistance arteries. BK impairment can lead to microvascular dysfunction and hemodynamic deficits in the brain.

Aryl hydrocarbon receptor (AhR) activation contributes to high-fat diet-induced vascular dysfunction.

Background And Purpose: Metabolic and vascular dysfunction are common features of obesity. Aryl hydrocarbon receptor (AhR) regulates lipid metabolism and vascular homeostasis, but whether vascular AhR are activated in obesity or have a protective and/or harmful effects on vascular function in obesity are unknown. Our study addresses whether AhR activation contributes to obesity-associated vascular dysfunction and the mechanisms involved in these AhR effects.

Blockade of protease-activated receptor 2 attenuates allergenmediated acute lung inflammation and leukocyte recruitment in mice.

Protease-activated receptor (PAR)2 has been implicated in mediating allergic airway inflammation.We investigate the role of PAR2 in lung inflammation and neutrophil and eosinophil recruitment into the lungs in amousemodel of shortterm acute allergic inflammation. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with the PAR2 antagonist ENMD1068 or with the PAR2-activating peptide (PAR2-AP) 1 hour before each OVA challenge.

Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation - implications in atherosclerosis.

Objective: The mechanisms involved in NOX5 activation in atherosclerotic processes are not completely understood. The present study tested the hypothesis that lysophosphatidylcholine (LPC), a proatherogenic component of oxLDL, induces endothelial calcium influx, which drives NOX5-dependent reactive oxygen species (ROS) production, oxidative stress, and endothelial cell dysfunction.

Approach: Human aortic endothelial cells (HAEC) were stimulated with LPC (10-5 M, for different time points).

Vascular Stress Signaling in Hypertension.

Cells respond to stress by activating a variety of defense signaling pathways, including cell survival and cell death pathways. Although cell survival signaling helps the cell to recover from acute insults, cell death or senescence pathways induced by chronic insults can lead to unresolved pathologies. Arterial hypertension results from chronic physiological maladaptation against various stressors represented by abnormal circulating or local neurohormonal factors, mechanical stress, intracellular accumulation of toxic molecules, and dysfunctional organelles.

Carotid sinus nerve stimulation attenuates alveolar bone loss and inflammation in experimental periodontitis.

Baroreceptor and chemoreceptor reflexes modulate inflammatory responses. However, whether these reflexes attenuate periodontal diseases has been poorly examined. Thus, the present study determined the effects of electrical activation of the carotid sinus nerve (CSN) in rats with periodontitis.

Evidence for the involvement of opioid and cannabinoid systems in the peripheral antinociception mediated by resveratrol.

Despite all the development of modern medicine, around 100 compounds derived from natural products were undergoing clinical trials only at the end of 2013. Among these natural substances in clinical trials, we found the resveratrol (RES), a pharmacological multi-target drug. RES analgesic properties have been demonstrated, although the bases of these mechanisms have not been fully elucidated.

Sex difference in GPER expression does not change vascular relaxation or reactive oxygen species generation in rat mesenteric resistance arteries.

Aim: An imbalance between antioxidant and pro-oxidant factors, with a predominance of the latter, characterises oxidative stress and is indicative of a loss of vascular function. The beneficial vascular effects of oestrogen may be related to its ability to stimulate the G protein-coupled oestrogen receptor (GPER) and produce antioxidant activity. This study evaluated the GPER-dependent relaxation response in the mesenteric resistance arteries of female and male rats and measured the contributions of pro-oxidant and antioxidant enzymes in this response.

Sodium butyrate modulates adipocyte expansion, adipogenesis, and insulin receptor signaling by upregulation of PPAR-γ in obese Apo E knockout mice.

Objectives: Studies suggest that sodium butyrate reduces obesity-associated inflammation and insulin resistance in in vitro and in vivo models. Apo E mice have high basal oxidative stress and naturally develop dyslipidemia and atherosclerosis. Because these disorders are present in obesity, the aim of this study was to determine whether Apo E mice could be a more realistic model for studying obesity and insulin resistance.

Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.

Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied.

Serca2a and Na(+)/Ca(2+) exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid.

Unlabelled: Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women.

Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats.

Main Methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20mg/kg/week for 4weeks); and NDE (trained and treated).