Pulmonary artery endothelial cells (PAECs) are a major contributor to hypoxic pulmonary hypertension (PH) due to the possible roles of reactive oxygen species (ROS). However, the molecular mechanisms and functional roles of ROS in PAECs are not well established. In this study, we first used Amplex UltraRed reagent to assess hydrogen peroxide (HO) generation.
View Article and Find Full Text PDFThe family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like () are commonly found in urban areas.
View Article and Find Full Text PDFHigh serum estrogen concentrations are associated with asthma development and severity, suggesting a link between estradiol and airway hyperresponsiveness (AHR). 17β-estradiol (E2) has non-genomic effects via Ca regulatory mechanisms; however, its effect on the plasma membrane Ca-ATPases (PMCA1 and 4) and sarcoplasmic reticulum Ca-ATPase (SERCA) is unknown. Hence, in the present study, we aim to demonstrate if E2 favors AHR by increasing intracellular Ca concentrations in guinea pig airway smooth muscle (ASM) through a mechanism involving Ca-ATPases.
View Article and Find Full Text PDFNumerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y and P2Y receptors and K channel opening.
View Article and Find Full Text PDFAirway smooth muscle (ASM) contraction is determined by the increase in intracellular Ca concentration ([Ca]) caused by its release from the sarcoplasmic reticulum (SR) or by extracellular Ca influx. Major channels involved in Ca influx in ASM cells are L-type voltage-dependent Ca channels (L-VDCCs) and nonselective cation channels (NSCCs). Transient receptor potential vanilloid 4 (TRPV4) is an NSCC recently studied in ASM.
View Article and Find Full Text PDFTheophylline is a drug commonly used to treat asthma due to its anti-inflammatory and bronchodilatory properties. Testosterone (TES) has been suggested to reduce the severity of asthma symptoms. This condition affects boys more than girls in childhood, and this ratio reverses at puberty.
View Article and Find Full Text PDFPulmonary hypertension (PH) is a devastating disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular failure and death. A major cellular response in this disease is the contraction of smooth muscle cells (SMCs) of the pulmonary vasculature. Cell contraction is determined by the increase in intracellular Ca2+ concentration ([Ca2+]i), which is generated and regulated by various ion channels.
View Article and Find Full Text PDFMitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases.
View Article and Find Full Text PDFTransient receptor potential (TRP) ion channels play critical roles in physiological and pathological conditions. Increasing evidence has unveiled the contribution of TRP vanilloid (TRPV) family in the development of asthma. The TRPV family is a group (TRPV1-TRPV6) of polymodal channels capable of sensing thermal, acidic, mechanical stress, and osmotic stimuli.
View Article and Find Full Text PDFInflammation is a characteristic marker in numerous lung disorders. Several immune cells, such as macrophages, dendritic cells, eosinophils, as well as T and B lymphocytes, synthetize and release cytokines involved in the inflammatory process. Gender differences in the incidence and severity of inflammatory lung ailments including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), lung cancer (LC), and infectious related illnesses have been reported.
View Article and Find Full Text PDFPulmonary hypertension (PH) is a progressive lung disease characterized by persistent pulmonary vasoconstriction. Another well-recognized characteristic of PH is the muscularization of peripheral pulmonary arteries. This pulmonary vasoremodeling manifests in medial hypertrophy/hyperplasia of smooth muscle cells (SMCs) with possible neointimal formation.
View Article and Find Full Text PDFAims: Ryanodine receptor-1 (RyR1) is essential for skeletal muscle cell functions. However, its roles in vascular smooth muscle cells (SMCs) are well recognized. This study aims to determine the potential physiological importance and difference in systemic and pulmonary artery SMCs (SASMCs and PASMCs).
View Article and Find Full Text PDFIntroduction: Androgen signaling comprises nongenomic and genomic pathways. Nongenomic actions are not related to the binding of the androgen receptor (AR) and occur rapidly. The genomic effects implicate the binding to a cytosolic AR, leading to protein synthesis.
View Article and Find Full Text PDFTacrolimus (TAC, also called FK506), a common immunosuppressive drug used to prevent allograft rejection in transplant patients, is well known to alter the functions of blood vessels. In this study, we sought to determine whether chronic treatment of TAC could inhibit the activity of big-conductance Ca-activated K (BK) channels in vascular smooth muscle cells (SMCs), leading to hypertension. Our data reveal that the activity of BK channels was inhibited in cerebral artery SMCs (CASMCs) from mice after intraperitoneal injection of TAC once a day for 4 weeks.
View Article and Find Full Text PDFAndrogens in asthmatic men may be linked to asthma severity, acting via nongenomic and genomic effects. This ailment affects boys more than girls during infancy, and this proportion reverses in puberty. Plasmatic androgen concentration in young men increases at this age and might be related to lower asthma symptoms.
View Article and Find Full Text PDFIt is known that mitochondrial reactive oxygen species generation ([ROS]) causes the release of Ca ryanodine receptor-2 (RyR2) on the sarcoplasmic reticulum (SR) in pulmonary artery smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary vasoconstriction (HPV). In this study, we sought to determine whether hypoxia-induced RyR2-mediated Ca release may in turn promote [ROS] in PASMCs and the underlying signaling mechanism. Our data reveal that application of caffeine or norepinephrine to induce Ca release increased [ROS] in PASMCs.
View Article and Find Full Text PDFIn airway smooth muscle, the intracellular basal Ca2+ concentration [b(Ca2+)i] must be tightly regulated by several mechanisms in order to maintain a proper airway patency. The b[Ca2+]i is efficiently regulated by sarcoplasmic reticulum Ca2+‑ATPase 2b, plasma membrane Ca2+‑ATPase 1 or 4 and by the Na+/Ca2+ exchanger. Membranal Ca2+ channels, including the L‑type voltage dependent Ca2+ channel (L‑VDCC), T‑type voltage dependent Ca2+ channel (T‑VDCC) and transient receptor potential canonical 3 (TRPC3), appear to be constitutively active under basal conditions via the action of different signaling pathways, and are responsible for Ca2+ influx to maintain b[Ca2+]i.
View Article and Find Full Text PDFAsthma symptoms have been associated with sex steroids. During childhood, this illness seems more frequent in boys than in girls and this tendency reverts in puberty when it is more severe in women. Testosterone (TES), at supraphysiological concentrations, relaxed pre-contracted airway smooth muscle, but its effects at physiological concentrations have not been thoroughly studied.
View Article and Find Full Text PDFUnlabelled: Testosterone (TES), other androgens and female sex steroids induce non-genomic rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17β-estradiol (E2) had a small effect. Blockers of L-type voltage dependent Ca channel (L-VDCC, D-600) and store operated Ca channel (SOC, 2-APB) also relaxed the basal tone.
View Article and Find Full Text PDFTumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues.
View Article and Find Full Text PDFIn adulthood, differentiation of precursor cells into neurons continues in several brain structures as well as in the olfactory neuroepithelium. Isolated precursors allow the study of the neurodevelopmental process in vitro. The aim of this work was to determine whether the expression of functional Voltage-Activated Ca(2+) Channels (VACC) is dependent on the neurodevelopmental stage in neuronal cells obtained from the human olfactory epithelium of a single healthy donor.
View Article and Find Full Text PDFUnlabelled: Membrane depolarization of airway smooth muscle (ASM) opens L-type voltage dependent Ca(2+) channels (L-VDCC) allowing Ca(2+) entrance to produce contraction. In Ca(2+) free conditions Na(+) permeates through L-VDCC in excitable and non-excitable cells and this phenomenon is annulled at µM Ca(2+) concentrations. Membrane depolarization also induces activation of Gq proteins and sarcoplasmic reticulum Ca(2+) release.
View Article and Find Full Text PDFSarcoplasmic reticulum Ca(2+) refilling (SRREF) is crucial to sustain the agonists induced airway smooth muscle contraction. Nevertheless, its mechanisms have not been clearly described yet, although L-type voltage dependent, store operated, receptor operated channels and the Na(+)/Ca(2+) exchanger in its reverse mode (NCXREV) have been proposed as Ca(2+) handling proteins participating in this process. We found that in guinea pig and bovine tracheal smooth muscle, SRREF induced by caffeine was completely abolished by thapsigargin, even in the presence of Bay K8644, an activator of the L-type Ca(2+) channel.
View Article and Find Full Text PDFThe Na(+)/Ca(2+)exchanger (NCX) principal function is taking 1 Ca(2+) out of the cytoplasm and introducing 3 Na(+). The increase of cytoplasmic Na(+) concentration induces the NCX reverse mode (NCX(REV)), favoring Ca(2+) influx. NCX(REV) can be inhibited by: KB-R7943 a non-specific compound that blocks voltage-dependent and store-operated Ca(2+) channels; SEA0400 that appears to be selective for NCX(REV), but difficult to obtain and SN-6, which efficacy has been shown only in cardiomyocytes.
View Article and Find Full Text PDFIn airway smooth muscle (ASM), ATP induces a contraction associated with the increase of [Ca(2+)](i). Cytosolic Ca(2+) is extruded to the extracellular space by the Na(+)/Ca(2+) exchanger (NCX) in its normal mode. Some agonists activate the reverse mode of the NCX (NCX(REV)), inducing Ca(2+) entry.
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