Modafinil exerts anti-inflammatory and anti-fibrotic effects by upregulating adenosine A and A receptors.

Adenosine receptor (AR) suppresses inflammation and fibrosis by activating cyclic adenosine monophosphate (cAMP) signaling. We investigated whether altered AR expression contributes to the development of fibrotic diseases and whether AAR and AAR upregulation inhibits fibrotic responses. Primary human lung fibroblasts (HLFs) from normal (NHLFs) or patients with idiopathic pulmonary fibrosis (DHLF) were used for in vitro testing.

Anti-inflammatory and anti-fibrotic effects of modafinil in nonalcoholic liver disease.

Small- and intermediate-conductance Ca-activated K channels, K2.3 and K3.1, are involved in cellular signaling processes associated with inflammation and fibrosis.

Internalization and Transportation of Endothelial Cell Surface K2.3 and K3.1 in Normal Pregnancy and Preeclampsia.

Altered redox state modulates the expression levels of endothelial K2.3 and K3.1 (Ks) in normal pregnancy (NP) and preeclampsia (PE), thereby regulating vascular contractility.

C1q/TNF-α-Related Protein 1 (CTRP1) Maintains Blood Pressure Under Dehydration Conditions.

Rationale: Circulating CTRP1 (C1q/TNF-α [tumor necrosis factor-α]-related protein 1) levels are increased in hypertensive patients compared with those in healthy subjects. Nonetheless, little is known about the molecular and physiological function of CTRP1 in blood pressure (BP) regulation.

Objective: To investigate the physiological/pathophysiological role of CTRP1 in BP regulation.

Altered Redox State Modulates Endothelial K2.3 and K3.1 Levels in Normal Pregnancy and Preeclampsia.

Aims: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial K2.3 and K3.

KCa 3.1 upregulation preserves endothelium-dependent vasorelaxation during aging and oxidative stress.

Endothelial oxidative stress develops with aging and reactive oxygen species impair endothelium-dependent relaxation (EDR) by decreasing nitric oxide (NO) availability. Endothelial KCa 3.1, which contributes to EDR, is upregulated by H2 O2 .

Lyso-globotriaosylceramide downregulates KCa3.1 channel expression to inhibit collagen synthesis in fibroblasts.

Fabry disease is an X-linked lysosomal storage disorder that is caused by a deficiency of α-galactosidase A. The disease ultimately manifests as multiple organ dysfunctions owing to excessive accumulation of globotriaosylceramide (Gb3). Among the several complications of Fabry disease, ascending thoracic aortic aneurysm is relatively common, which is classically associated with connective tissue disorders characterized by abnormal defects or deficiencies in structural proteins such as collagen and elastin.

Altering sphingolipid composition with aging induces contractile dysfunction of gastric smooth muscle via K(Ca) 1.1 upregulation.

K(Ca) 1.1 regulates smooth muscle contractility by modulating membrane potential, and age-associated changes in K(Ca) 1.1 expression may contribute to the development of motility disorders of the gastrointestinal tract.

Isolation and in vitro culture of vascular endothelial cells from mice.

In cardiovascular disorders, understanding of endothelial cell (EC) function is essential to elucidate the disease mechanism. Although the mouse model has many advantages for in vivo and in vitro research, efficient procedures for the isolation and propagation of primary mouse EC have been problematic. We describe a high yield process for isolation and in vitro culture of primary EC from mouse arteries (aorta, braches of superior mesenteric artery, and cerebral arteries from the circle of Willis).

Retnla overexpression attenuates allergic inflammation of the airway.

Resistin-like molecule alpha (Retnla), also known as 'Found in inflammatory zone 1', is a secreted protein that has been found in bronchoalveolar lavage (BAL) fluid of ovalbumin (OVA)-induced asthmatic mice and plays a role as a regulator of T helper (Th)2-driven inflammation. However, the role of Retnla in the progress of Th2-driven airway inflammation is not yet clear. To better understand the function of Retnla in Th2-driven airway inflammation, we generated Retnla-overexpressing (Retnla-Tg) mice.

Globotriaosylceramide induces lysosomal degradation of endothelial KCa3.1 in fabry disease.

Objective: Globotriaosylceramide (Gb3) induces KCa3.1 downregulation in Fabry disease (FD). We investigated whether Gb3 induces KCa3.

Contradictory Effects of Superoxide and Hydrogen Peroxide on KCa3.1 in Human Endothelial Cells.

Reactive oxygen species (ROS) are generated in various cells, including vascular smooth muscle and endothelial cells, and regulate ion channel functions. KCa3.1 plays an important role in endothelial functions.

The essential oil of Citrus bergamia Risso induces vasorelaxation of the mouse aorta by activating K(+) channels and inhibiting Ca(2+) influx.

Objectives: The aim of this study was to explore the effect of the essential oil of Citrus bergamia Risso (bergamot) on mouse blood vessels and to analyse the mechanism of this effect from a pharmacological perspective.

Methods: We investigated the effect of bergamot essential oil (BEO) on vascular tonus during contraction of mouse aorta induced by prostaglandin F2α (PGF2α ) or noradrenaline (norepinephrine).

Key Findings: In mouse aortic rings, BEO (0.

Irbit mediates synergy between ca(2+) and cAMP signaling pathways during epithelial transport in mice.

Background & Aims: The cyclic adenosine monophosphate (cAMP) and Ca(2+) signaling pathways synergize to regulate many physiological functions. However, little is known about the mechanisms by which these pathways interact. We investigated the synergy between these signaling pathways in mouse pancreatic and salivary gland ducts.

NADPH oxidase 2-derived superoxide downregulates endothelial KCa3.1 in preeclampsia.

Endothelial dysfunction is associated with KCa3.1 dysfunction and contributes to the development of hypertension in preeclampsia. However, evidence of endothelial KCa3.

Modafinil inhibits K(Ca)3.1 currents and muscle contraction via a cAMP-dependent mechanism.

Modafinil has been used as a psychostimulant for the treatment of narcolepsy. However, its primary mechanism of action remains elusive. Therefore, we examined the effects of modafinil on K(Ca)3.

Globotriaosylceramide leads to K(Ca)3.1 channel dysfunction: a new insight into endothelial dysfunction in Fabry disease.

Aims: Excessive endothelial globotriaosylceramide (Gb3) accumulation is associated with endothelial dysfunction and impaired endothelium-dependent relaxation in Fabry disease. In endothelial cells, K(Ca)3.1 channels contribute to endothelium-dependent relaxation.

Immobilization stress induces endothelial dysfunction by oxidative stress via the activation of the angiotensin II/its type I receptor pathway.

Objective: Psychological stress has been shown to contribute to the development of atherosclerosis; however its underlying mechanism has not been clearly elucidated. We here studied the mechanism by which immobilization stress causes endothelial dysfunction with specific aim of identifying the role of angiotensin II and its type I (AT(1)) receptor signaling pathway.

Methods And Results: Rats (n=30) were subjected to immobilization stress (120 min/day) for 14 days using a restrainer.

Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats.

Aim Of The Study: The purpose of the present study was to screen aromatic essential oils that have antidepressant effects to identify the regulatory mechanisms of selected essential oils.

Materials And Methods: The antidepressant effects of essential oils of Anthemis nobilis (chamomile), Salvia sclarea (clary sage; clary), Rosmarinus officinalis (rosemary), and Lavandula angustifolia (lavender) were assessed using a forced swim test (FST) in rats. Rats were treated with essential oils by intraperitoneal injection or inhalation.

Modulation of nonselective cation current by oxidized LDL and lysophosphatidylcholine and its inhibitory contribution to endothelial damage.

Aims: This study examined the effects of oxidized low-density lipoprotein (LDL) and its major lipid constituent lysophosphatidylcholine (LPC) on nonselective cation (NSC) current and its inhibitory contribution to LPC-induced cytotoxicity in cultured human umbilical endothelial cells (HUVECs).

Main Methods: Patch-clamp technique and the resazurin-based cell viability assay were used.

Key Findings: In voltage-clamped cells, oxidized LDL or LPC slowly activated NSC current.

Superoxide generated by lysophosphatidylcholine induces endothelial nitric oxide synthase downregulation in human endothelial cells.

We examined the mechanism through which lysophosphatidylcholine (LPC) induces endothelial nitric oxide (eNOS) downregulation. Human umbilical vein endothelial cells (HUVECs) were treated with LPC (50-150 microM) for 0.5-2 h or the reactive oxygen species (ROS) donors, xanthine/xanthine oxidase (X/XO), 1,4-hydroquinone (HQ) or tert-butylhydroperoxide (TBHP) for 2 h.

Oxidized Low-density Lipoprotein- and Lysophosphatidylcholine-induced Ca Mobilization in Human Endothelial Cells.

The effects of oxidized low-density lipoprotein (OxLDL) and its major lipid constituent lysophosphatidylcholine (LPC) on Ca(2+) entry were investigated in cultured human umbilical endothelial cells (HUVECs) using fura-2 fluorescence and patch-clamp methods. OxLDL or LPC increased intracellular Ca(2+) concentration ([Ca(2+)](i)), and the increase of [Ca(2+)](i) by OxLDL or by LPC was inhibited by La(3+) or heparin. LPC failed to increase [Ca(2+)](i) in the presence of an antioxidant tempol.

Lysophosphatidylcholine induces endothelial cell injury by nitric oxide production through oxidative stress.

Objective: To determine whether lysophosphatidylcholine (LPC) induces endothelial cell injury by altering the production of nitric oxide (NO) and thereby increasing reactive oxygen species (ROS).

Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to LPC, LPC with N(G)-nitro-l-arginine methyl ester (L-NAME), LPC with antioxidants. LPC-induced cell injury and viability were determined using LDH and Resazurin assays.

Intracellular Na(+) modulates large conductance Ca(2+)-activated K (+) currents in human umbilical vein endothelial cells.

We studied the effects of Na(+) influx on large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in cultured human umbilical vein endothelial cells (HUVECs) by means of patch clamp and SBFI microfluorescence measurements. In current-clamped HUVECs, extracellular Na(+) replacement by NMDG(+) or mannitol hyperpolarized cells. In voltage-clamped HUVECs, changing membrane potential from 0 mV to negative potentials increased intracellular Na(+) concentration ([Na(+)](i)) and vice versa.

The Na(+)/Ca(2+) exchanger inhibitor KB-R7943 activates large-conductance Ca(2+)-activated K(+) channels in endothelial and vascular smooth muscle cells.

The effect of the selective inhibitor of Na(+)/Ca(2+) exchanger (NCX), KB-R7943, on large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels was examined in cultured human umbilical vein endothelial cells (HUVECs) and freshly isolated mouse aortic smooth muscle cells (MASMCs). In voltage-clamped cells, KB-R7943 reversibly activated BK(Ca) currents in HUVECs and MASMCs. The EC(50) of KB-R7943 for BK(Ca) current activation in HUVECs was determined to be 6.