We have previously shown that hydrogen sulfide (H 2 S) reduces myogenic tone and causes relaxation of phenylephrine (PE)-constricted mesenteric arteries. This effect H S to cause vasodilation vascular smooth muscle cell (VSMC) hyperpolarization was mediated by large-conductance Ca 2+ -activated potassium channels (BK ). sparks are ryanodine receptor (RyR)-mediated -release events activate BK in VSMCs membrane vasodilation. hypothesized activates small were measured using confocal microscopy...

Physiological responses to chronic hypoxia include polycythemia, pulmonary arterial remodeling, and vasoconstriction. Chronic causes hypertension leading right ventricular hypertrophy heart failure. During hypertension, arteries exhibit increased expression of smooth muscle-α-actin -myosin heavy chain. NFATc3 (nuclear factor activated T cells isoform c3), which is aCa2+-dependent transcription factor, has been recently linked muscle phenotypic maintenance through the regulation α-actin. The...

Myogenic tone, an important regulator of vascular resistance, is dependent on smooth muscle (VSM) depolarization, can be modulated by endothelial factors, and increased in several models hypertension. Intermittent hypoxia (IH) elevates blood pressure causes dysfunction. Hydrogen sulfide (H(2)S), a recently described endothelium-derived vasodilator, produced the enzyme cystathionine γ-lyase (CSE) acts hyperpolarizing VSM.Determine whether IH decreases H(2)S production to increase myogenic...

Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution adaptive immune system not well characterized hypertension caused chronic hypoxia. CD4 + cells are required for initiating maintaining inflammation, suggesting that these could play an important role pathogenesis hypoxic hypertension. Our objective was to test hypothesis specifically...

Hyperglycemia is a recognized risk factor for cardiovascular disease in diabetes. Recently, we reported that high glucose activates the Ca(2+)/calcineurin-dependent transcription nuclear of activated T cells (NFAT) arteries ex vivo. Here, sought to determine whether hyperglycemia NFAT vivo and this leads vascular complications.An intraperitoneal glucose-tolerance test mice increased NFATc3 accumulation smooth muscle. Streptozotocin-induced diabetes resulted transcriptional activity...

Air pollutant levels positively correlate with increases in both acute and chronic cardiovascular disease. The diesel exhaust (DE) endothelin (ET) levels, suggesting that this peptide may contribute to DE-induced We hypothesized exposure DE also enhances ET-1-mediated coronary artery constrictor sensitivity. Constrictor responses KCl, U-46619, ET-1 were recorded by videomicroscopy pressurized intraseptal arteries from rats exposed for 5 h (300 microg/m(3)) or filtered air (Air). constriction...

Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca 2+ -dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated hypoxia-induced pulmonary arterial remodeling adult mice. Therefore, we hypothesized that NFATc3 is required for neonatal aim this study was determine whether 1) mediates increases right ventricular systolic pressure mice; 2) mice exposed hypoxia; 3) involved hypertrophy...

AUTHOR SUMMARY The host-pathogen interface is a biological niche in which two entities competes for essential resources. host’s nutritional immunity restrict access to metals, while successful pathogen overcomes these restrictions using dedicated uptake pathways. Pseudopaline high-affinity metallophore allowing Pseudomonas aeruginosa acquire zinc chelated environments. We demonstrate that this pathway the last-resort solution dreadful pathogen. capacity provide metal zinc-metalloproteins...

Background: Acid-sensing ion channel 1a (ASIC1a) is an H+-gated cation that responds to extracellular acidosis in both normal and pathological states, including ischemia, inflammation, metabolic disturbances. While ASIC1a regulates vascular reactivity, its role blood pressure regulation remains unclear, particularly concerning sex, aging, disease. This study aims investigate whether ASIC1a: 1) contributes cardiovascular function a sex-dependent manner; 2) plays dynamic homeostasis with...

Although largely distinct and seemingly unrelated, asthma pulmonary arterial hypertension (PAH) have important pathological features in common, including inflammation, smooth muscle contraction remodelling. We hypothesised that these common could be explained by one shared mechanism of pathogenesis: activation the transcription factor NFAT (nuclear activated T-cells). If this concept is validated, it lead to introduction novel therapeutic strategies against both lung disorders. In several...

Elevated reactive oxygen species are implicated in pulmonary hypertension (PH). Superoxide dismutase (SOD) limits superoxide bioavailability, and decreased SOD activity is associated with PH. A decrease expected to increase reduce hydrogen peroxide levels. Such an imbalance of superoxide/hydrogen has been as a mediator nuclear factor activated T cells (NFAT) activation epidermal cells. We have shown that NFATc3 required for chronic hypoxia-induced However, it unknown whether the circulation...

Interleukin-6 (IL-6) is a pleotropic cytokine that signals through the membrane-bound IL-6 receptor (mIL-6R) to induce anti-inflammatory ("classic-signaling") responses. This also binds soluble IL-6R (sIL-6R) promote inflammation ("trans-signaling"). mIL-6R expression restricted hepatocytes and immune cells. Activated T cells release sIL-6R into adjacent tissues trans-signaling. These cellular actions require ubiquitously expressed membrane gp130. Reports show produced by pulmonary arterial...

Expression of alpha-actin in smooth muscle cells (SMCs) is regulated, part, by an intronic serum response factor (SRF)-binding CArG element. We have identified a conserved nuclear activated T (NFAT) binding site that overlaps this box and tested the hypothesis plays previously unrecognized role regulating expression. A reporter construct prepared using 56-bp region mouse first intron containing SRF, NFAT, AP-1 sites (SNAP) acted as enhancer element context minimal thymidine kinase promoter....

The transcription factor NFAT (nuclear of activated T-cells) is implicated in cardiac hypertrophy and vasculogenesis. activation, reflecting dephosphorylation by the calcium-dependent phosphatase, calcineurin, subsequent nuclear localization, generally thought to require a sustained increase intracellular calcium. However, smooth muscle we have found that elevation calcium membrane depolarization fails induce an localization NFATc3 isoform. Here, demonstrate physiological intravascular...

Chronic hypoxia (CH) activates the Ca 2+ -dependent transcription factor nuclear of activated T cells isoform c3 (NFATc3) in mouse pulmonary arteries. However, mechanism this response has not been explored. Since we have demonstrated that NFATc3 is required for CH-induced arterial remodeling, establishing how CH physiologically significant. The goal study was to test hypothesis endothelin-1 (ET-1) contributes activation. We propose requires increased smooth muscle cell (PASMC) intracellular...

Abstract —The aim of the present study was to determine relationship between hypotensive effect atrial natriuretic peptide (ANP) and nitric oxide (NO) pathway. N G -nitro- l -arginine methyl ester bolus (L-NAME, 1 mg/kg) reverted decrease in mean arterial pressure induced by ANP administration (5 μg/kg 0.2 μg · kg −1 min infusion), injection L-NAME before suppressed response. To confirm these findings, a histochemical reaction used NADPH-diaphorase activity (a NO synthase marker) endothelium...

The transcription factor NFAT (nuclear of activated T-cells) is a cytosolic phosphoprotein that accumulates in the nucleus following dephosphorylation by calcium (Ca2+)/calmodulin-dependent phosphatase, calcineurin. A defining feature stimuli induce nuclear accumulation/activation sustained increase global intracellular Ca2+. Contrary to expectations, we have found elevation Ca2+, induced membrane potential depolarization and mediated voltage-dependent Ca2+ channels, does not result...

Sleep apnea, defined as intermittent respiratory arrest during sleep, is associated with increased incidence of hypertension and peripheral vascular disease. Exposure rodents to brief periods hypercarbia/hypoxia (H-IH) sleep mimics the cyclical hypoxia-normoxia apnea. Endothelin-1, an upstream activator nuclear factor activated T cells (NFAT), H-IH. Therefore, we hypothesized that NFATc3 by H-IH required for H-IH-induced hypertension. Consistent this hypothesis, found (20 exposures per hour...

The systemic vasculature exhibits attenuated vasoconstriction following hypobaric chronic hypoxia (CH) that is associated with endothelium-dependent vascular smooth muscle (VSM) cell hyperpolarization. We hypothesized increased activity of endothelial (EC) large-conductance, calcium-activated potassium (BK(Ca)) channels contributes to this response. Gracilis resistance arteries from CH (barometric pressure = 380 mmHg for 48 h) rats demonstrated reduced myogenic reactivity and hyperpolarized...

Our laboratory shows that acid-sensing ion channel 1 (ASIC1) contributes to the development of hypoxic pulmonary hypertension by augmenting store-operated Ca(2+) entry (SOCE) is associated with enhanced agonist-induced vasoconstriction and arterial remodeling. However, this influx following chronic hypoxia (CH) not dependent on an increased ASIC1 protein expression in smooth muscle cells (PASMC). It well documented changes redox potential reactive oxygen species homeostasis. a...

The imbalance between pro-inflammatory T helper 17 (T H 17) cells and anti-inflammatory regulatory (Tregs) has been implicated in multiple inflammatory autoimmune conditions, but the effects of chronic hypoxia (CH) on this balance have yet to be explored. CH-exposed mice an increased prevalence lungs with no change Tregs. This is significant because it precedes development pulmonary hypertension (PH), are a major contributor CH-induced PH. While Tregs shown attenuate or prevent certain types...

The calcium-dependent transcription factor NFATc3, which is a member of the nuclear activated T cells (NFAT) family factors, critical for embryonic vascular development and differentiation. Despite its potential importance, nothing known about NFATc3 regulation in brain microcirculation. In present study, we sought to investigate role that glutamate, possibly through astrocytic communication, plays control pericytes from parenchymal microvessels. Coronal cortical slices neonatal rats were...

Sleep apnea (SA) is defined as intermittent respiratory arrest during sleep and affects up to 20% of the adult population. SA also associated with an increased incidence hypertension peripheral vascular disease. Exposing rodents hypoxia mimics cyclical hypoxia/normoxia SA. We have previously shown that in mice rats induces ET-1 upregulation systemic hypertension. Furthermore, (IH) increases nuclear factor activated T cells isoform 3 (NFATc3) transcriptional activity aorta mesenteric...