Isolation of Endothelial Cells from Human Internal Mammary Artery.

Endothelial cells are a major contributor to cardiovascular diseases. Studying their function and how they influence pathological processes remains an ongoing area of research. Although primary endothelial cells might be readily available from animals, translating results from these studies can be challenging due to species-dependent differences.

Mini Review: the non-neuronal cardiac cholinergic system in type-2 diabetes mellitus.

Diabetic heart disease remains the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Both insulin resistance and metabolic derangement, hallmark features of T2DM, develop early and progressively impair cardiovascular function. These factors result in altered cardiac metabolism and energetics, as well as coronary vascular dysfunction, among other consequences.

Retraction notice to "Non-neuronal cholinergic system delays cardiac remodelling in type 1 diabetes" [Heliyon 9 (2023) e17434].

[This retracts the article DOI: 10.1016/j.heliyon.

Non-neuronal cholinergic system delays cardiac remodelling in type 1 diabetes.

Aims: Type 1 diabetes mellitus (T1DM) is associated with increased risk of cardiovascular disease (CVD) and mortality. The underlying mechanisms for T1DM-induced heart disease still remains unclear. In this study, we aimed to investigate the effects of cardiac non-neuronal cholinergic system (cNNCS) activation on T1DM-induced cardiac remodelling.

Vasopressin regulation of maternal body fluid balance in pregnancy and lactation: A role for TRPV channels?

Renal water reabsorption increases in pregnancy and lactation to expand maternal blood volume to cope with the cardiovascular demands of the developing fetus and new-born baby. Vasopressin (antidiuretic hormone) promotes renal water reabsorption and its secretion is principally stimulated by body fluid osmolality. Hence, lowered osmolality normally decreases vasopressin secretion.

COVID-19 and Liquid Homeostasis in the Lung-A Perspective through the Epithelial Sodium Channel (ENaC) Lens.

Infections with a new corona virus in 2019 lead to the definition of a new disease known as Corona Virus Disease 2019 (COVID-19). The sever cases of COVID-19 and the main cause of death due to virus infection are attributed to respiratory distress. This is associated with the formation of pulmonary oedema that impairs blood oxygenation and hypoxemia as main symptoms of respiratory distress.

Epithelial Sodium Channel δ Subunit Is Expressed in Human Arteries and Has Potential Association With Hypertension.

Background: Elevated expression and increased activity of vascular epithelial sodium channel (ENaC) can result in vascular dysfunction in small animal models. However, there is limited or no knowledge on expression and function of ENaC channels in human vasculature. Hence, this study explored the expression and function of ENaC in human arteries and their association with hypertension.

Epithelial Na+ channel and the glycocalyx: a sweet and salty relationship for arterial shear stress sensing.

Purpose Of Review: The ability of endothelial cells to sense mechanical force, and shear stress in particular, is crucial for normal vascular function. This relies on an intact endothelial glycocalyx that facilitates the production of nitric oxide (NO). An emerging arterial shear stress sensor is the epithelial Na+ channel (ENaC).

Plasticity in Intrinsic Excitability of Hypothalamic Magnocellular Neurosecretory Neurons in Late-Pregnant and Lactating Rats.

Oxytocin and vasopressin secretion from the posterior pituitary gland are required for normal pregnancy and lactation. Oxytocin secretion is relatively low and constant under basal conditions but becomes pulsatile during birth and lactation to stimulate episodic contraction of the uterus for delivery of the fetus and milk ejection during suckling. Vasopressin secretion is maintained in pregnancy and lactation despite reduced osmolality (the principal stimulus for vasopressin secretion) to increase water retention to cope with the cardiovascular demands of pregnancy and lactation.

Enhanced Shear Force Responsiveness of Epithelial Na Channel's (ENaC) δ Subunit Following the Insertion of N-Glycosylation Motifs Relies on the Extracellular Matrix.

Members of the Degenerin/epithelial Na channel (ENaC) protein family and the extracellular cell matrix (ECM) form a mechanosensitive complex. A core feature of this complex are tethers, which connect the channel with the ECM, however, knowledge about the nature of these tethers is scarce. N-glycans of α ENaC were recently identified as potential tethers but whether N-glycans serve as a ubiquitous feature for mechanosensation processes remains unresolved.

Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.

Background: Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (MAChR) to synthesize, release, degrade ACh as well as for ACh to transduce a signal. NNCS is linked to cardiac cell survival, angiogenesis and glucose metabolism.

The subunit of epithelial sodium channel in humans-a potential player in vascular physiology.

Vascular epithelial sodium channels (ENaCs) made up of canonical α, β, and γ subunits have attracted more attention recently owing to their physiological role in vascular health and disease. A fourth subunit, δ-ENaC, is expressed in various mammalian species, except mice and rats, which are common animal models for cardiovascular research. Accordingly, δ-ENaC is the least understood subunit.

Nicotine stimulates ion transport via metabotropic β4 subunit containing nicotinic ACh receptors.

Background And Purpose: Mucociliary clearance is an innate immune process of the airways, essential for removal of respiratory pathogens. It depends on ciliary beat and ion and fluid homeostasis of the epithelium. We have shown that nicotinic ACh receptors (nAChRs) activate ion transport in mouse tracheal epithelium.

Epithelial Na Channel (ENaC) Formed by One or Two Subunits Forms Functional Channels That Respond to Shear Force.

Canonical epithelial sodium channels (ENaCs) are heterotrimers formed by α, β, and γ ENaC subunits in vertebrates and belong to the Degenerin/ENaC family of proteins. Proteins from this family form mechanosensitive channels throughout the animal kingdom. Activity of canonical ENaC is regulated by shear force (SF) mediating Na absorption in the kidney and vascular tone of arteries.

Shear force sensing of epithelial Na channel (ENaC) relies on -glycosylated asparagines in the palm and knuckle domains of αENaC.

Mechanosensitive ion channels are crucial for normal cell function and facilitate physiological function, such as blood pressure regulation. So far little is known about the molecular mechanisms of how channels sense mechanical force. Canonical vertebrate epithelial Na channel (ENaC) formed by α-, β-, and γ-subunits is a shear force (SF) sensor and a member of the ENaC/degenerin protein family.

Shear force modulates the activity of acid-sensing ion channels at low pH or in the presence of non-proton ligands.

Acid-sensing ion channels (ASICs) belong to the degenerin/epithelial sodium channel protein family that form mechanosensitive ion channels. Evidence as to whether or not ASICs activity is directly modulated by mechanical force is lacking. Human ASICs (hASIC1, hASIC2a and hASIC3a) were heterologously expressed as homomeric channels in Xenopus oocytes and two-electrode voltage-clamp recordings were performed.

The non-neuronal cholinergic system in the heart: A comprehensive review.

The autonomic influences on the heart have a ying-yang nature, albeit oversimplified, the interplay between the sympathetic and parasympathetic system (known as the cholinergic system) is often complex and remain poorly understood. Recently, the heart has been recognized to consist of neuronal and non-neuronal cholinergic system (NNCS). The existence of cardiac NNCS has been confirmed by the presence of cholinergic markers in the cardiomyocytes, which are crucial for synthesis (choline acetyltransferase, ChAT), storage (vesicular acetylcholine transporter, VAChT), reuptake of choline for synthesis (high-affinity choline transporter, CHT1) and degradation (acetylcholinesterase, AChE) of acetylcholine (ACh).

Epithelial Na channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice.

A potential "new player" in arteries for mediating shear stress responses is the epithelial Na channel (ENaC). The contribution of ENaC as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance), is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (third-order mesenteric) arteries isolated from C57Bl/6J mice.

Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na channels (ENaCs).

Background: Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd ions. Gd is also a modulator of mechano-gated ion channels, including the epithelial Na channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd from GBCAs causing the above-mentioned adverse reactions.

Mechanosensitive activation of CFTR by increased cell volume and hydrostatic pressure but not shear stress.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-) channel that is essential for electrolyte and fluid homeostasis. Preliminary evidence indicates that CFTR is a mechanosensitive channel. In lung epithelia, CFTR is exposed to different mechanical forces such as shear stress (Ss) and membrane distention.

Luminal acetylcholine does not affect the activity of the CFTR in tracheal epithelia of pigs.

Fluid homeostasis mediated by the airway epithelium is required for proper lung function, and the CFTR (cystic fibrosis transmembrane conductance regulator) Cl(-) channel is crucial for these processes. Luminal acetylcholine (ACh) acts as an auto-/paracrine mediator to activate Cl(-) channels in airway epithelia and evidence exists showing that nicotinic ACh receptors activate CFTR in murine airway epithelia. The present study investigated whether or not luminal ACh regulates CFTR activity in airway epithelia of pigs, an emerging model for investigations of human airway disease and cystic fibrosis (CF) in particular.

Phosphocholine-Modified Macromolecules and Canonical Nicotinic Agonists Inhibit ATP-Induced IL-1β Release.

IL-1β is a potent proinflammatory cytokine of the innate immune system that is involved in host defense against infection. However, increased production of IL-1β plays a pathogenic role in various inflammatory diseases, such as rheumatoid arthritis, gout, sepsis, stroke, and transplant rejection. To prevent detrimental collateral damage, IL-1β release is tightly controlled and typically requires two consecutive danger signals.

Controlling epithelial sodium channels with light using photoswitchable amilorides.

Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs). These heterotrimeric transmembrane proteins, assembled from β, γ and α or δ subunits, effectively control water transport across epithelia and sodium influx into non-epithelial cells. The functional role of δβγENaC in various organs, including the human brain, is still poorly understood and no pharmacological tools are available for the functional differentiation between α- and δ-containing ENaCs.

Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes.

Chemosensory cells in the mucosal surface of the respiratory tract ("brush cells") use the canonical taste transduction cascade to detect potentially hazardous content and trigger local protective and aversive respiratory reflexes on stimulation. So far, the urogenital tract has been considered to lack this cell type. Here we report the presence of a previously unidentified cholinergic, polymodal chemosensory cell in the mammalian urethra, the potential portal of entry for bacteria and harmful substances into the urogenital system, but not in further centrally located parts of the urinary tract, such as the bladder, ureter, and renal pelvis.

Evidence for expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells.

There is a growing evidence that the peptide hormone angiotensin II (ANGII) can act as an auto-/paracrine mediator to regulate epithelial ion transport processes. The present study focused on the impact of ANGII on transepithelial ion transport in pulmonary epithelia. Transcripts for the ANGII receptor type 1 (ATR1) were detected in lungs of Xenopus laevis and H441 cells (human pulmonary epithelial cell line).