Chronic hypoxic pulmonary hypertension is associated with profound vascular remodeling and alterations in Ca 2+ homeostasis arterial smooth muscle cells (PASMCs). Recent studies show that transient receptor potential (TRPC) genes, which encode store-operated receptor-operated cation channels, play important roles regulation cell proliferation. However, the influence of chronic hypoxia on TRPC channels has not been determined. Here we compared expression, store- entries PASMCs normoxic rats....

Transient receptor potential melastatin- (TRPM) and vanilloid-related (TRPV) channels are nonselective cation pertinent to diverse physiological functions. Multiple TRPM TRPV channel subtypes have been identified cloned in different tissues. However, their information vascular tissue is scant. In this study, we sought identify expressed rat deendothelialized intralobar pulmonary arteries (PAs) aorta. With RT-PCR, mRNA of TRPM2, TRPM3, TRPM4, TRPM7, TRPM8 family TRPV1, TRPV2, TRPV3, TRPV4...

Reactive oxygen species (ROS) generated from NADPH oxidases and mitochondria have been implicated as key messengers for pulmonary vasoconstriction vascular remodeling induced by agonists hypoxia. Since Ca(2+) mobilization is essential cell proliferation, we sought to characterize the response delineate pathways activated hydrogen peroxide (H(2)O(2)) in rat intralobar arterial smooth muscle cells (PASMCs). Exogenous application of 10 microM 1 mM H(2)O(2) elicited concentration-dependent...

Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca 2+ homeostasis pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated store-operated entry (SOCE) augmented PASMCs of chronic hypoxic rats patients (PAH). Here we further examine the involvement TRPC SOCE PH a widely used rat model monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular...

Pulmonary arterial hypertension (PAH) is a severe and debilitating disease characterized by remodeling of the pulmonary vessels, which driven excessive proliferation migration apoptosis resistance in artery smooth muscle cells (PASMCs). The calcineurin (CaN)/nuclear factor activated T-cells (NFAT) signaling pathway most important downstream store-operated Ca2+ entry (SOCE), increased PAH. CaN/NFAT has been reported to contribute abnormal chronic hypoxia (CH)-induced However, effect on PASMC...

Ryanodine receptors (RyRs) of pulmonary arterial smooth muscle cells (PASMCs) play important roles in major physiological processes such as hypoxic vasoconstriction and perinatal vasodilatation. Recent studies show that three subtypes RyRs are coexpressed RyR-gated Ca2+ stores distributed heterogeneously systemic vascular myocytes. However, the molecular identity subcellular distribution have not been examined PASMCs. In this study we detected mRNA proteins all rat intralobar PASMCs using...

Ca + sparks originating from ryanodine receptors (RyRs) are known to cause membrane hyperpolarization and vasorelaxation in systemic arterial myocytes. By contrast, we have found that 2+ of pulmonary smooth muscle cells (PASMCs) associated with depolarization activated by endothelin-1 (ET-1), a potent vasoconstrictor mediates/modulates acute chronic hypoxic vasoconstriction. In this study, characterized the effects ET-1 on physical properties probed signal transduction mechanism for spark...

Pulmonary hypertension (PH) is characterized by profound vascular remodeling and altered Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Magnesium ion (Mg2+), a natural antagonist cofactor for numerous enzymes, crucial regulating diverse cellular functions, but its roles PH remains unclear. Here, we examined the of Mg2+ transporters development. Chronic hypoxia monocrotaline induced significant adult male rats. It was associated with reduction [Mg2+]i PASMCs, increase...

Background: Pulmonary arterial hypertension maintains rapid cell proliferation and vascular remodeling through metabolic reprogramming. Recent studies suggested that circRNAs play important role in pulmonary smooth muscle cells proliferation. However, the relationship between circRNA, proliferation, reprogramming has not been investigated. Methods: RNA-seq qRT-PCR reveal differential expression profile of circRNA arteries rat models. Transfection was used to examine effects circSMOC1 on...

Background: Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure death. Despite several treatments are available, many forms of PH still incurable. Ginsenoside Rb1, a principle active ingredient Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, suppresses monocrotaline (MCT)-induced hypertrophy. However, its effect the pulmonary functions related...

Chloride channels at the apical membrane of intestinal epithelial cells are involved in excessive fluid secretion diarrhea and diminished cystic fibrosis (CF). Diarrhea induced by heat-stable toxin from Escherichia coli is associated with elevated guanosine 3',5'-cyclic monophosphate (cGMP) cells, but it unknown whether chloride regulated cGMP directly or via cGMP-dependent protein kinase (PKG). Single-channel recordings (inside-out excised patches) T84 reveal a 10-pS channel linear...

Background: Pulmonary hypertension (PH) is characterized by profound vascular remodeling and alterations in Ca2+ homeostasis pulmonary arterial smooth muscle cells (PASMCs). Multiple transient receptor potential melastatin-related (TRPM) subtypes have been identified tissue. However, the changes expression function of TRPM channels not detail. Methods: We examined functions altered two widely used rat models chronic hypoxia (CH)- monocrotaline (MCT)-induced PH. Results: CH-exposed...

Pulmonary artery hypertension (PAH), which is characterized by an increase in pulmonary circulation blood pressure, a fatal disease, and its pathogenesis remains unclear.In this study, RNA sequencing (RNA-seq), tandem mass tags (TMT) reduced representation bisulfite (RRBS) were performed to detect the levels of mRNA, protein, DNA methylation arteries (PAs), respectively. To screen possible pathways proteins related PAH, pathway enrichment analysis protein-protein interaction (PPI) network...

5-Hydroxytryptamine (5-HT)-dependent signaling mediated through its transporters and receptors plays important roles in chronic hypoxic pulmonary hypertension (CHPH), which is associated with aberrant reactive oxygen species (ROS) production. NADPH oxidase 4 (NOX4) one of the major sources ROS vasculature, has been implicated development PH. NOX4 generates H2O2, can activate transient receptor potential melastatin 2 (TRPM2) channels, providing Ca2+ signals for cell proliferation migration....

Clinical evidence revealed abnormal prevalence of coronary artery (CA) disease in patients with pulmonary hypertension (PH). The mechanistic connection between PH and CA is unclear. Serotonin (5-hydroxytryptamine), reactive oxygen species, Ca

New Findings What is the central question of this study? The goal study was to elucidate role magnesium in regulation pulmonary vascular reactivity relationship hypoxic hypertension. main finding and its importance? We found that essential for normal vasoreactivity artery. Increasing concentration attenuates vasoconstriction improves vasodilatation via release nitric oxide. Pulmonary hypertension associated with endothelial dysfunction resulting suppression modulation vasodilatation. These...

Store-operated Ca2+ entry (SOCE) contributes to a multitude of physiological and pathophysiological functions in pulmonary vasculatures. SOCE attributable inositol 1,4,5-trisphosphate receptor (InsP3R)-gated store has been studied extensively, but the role ryanodine (RyR)-gated remains unclear. The present study aims delineate relationship between RyR-gated stores SOCE, characterize properties artery smooth muscle cells (PASMCs). PASMCs were isolated from intralobar arteries male Wister...

Malignant hyperthermia (MH) is a pharmacogenetic disease of humans and various animal species that predisposes to life-threatening, anesthetic agent-induced syndrome. MH thought be consequence abnormal, sustained increases in myoplasmic Ca++ sarcoplasmic reticulum (SR) membranes from muscle have been shown release channel defect. In the present study we tested hypothesis abnormal mechanism can expressed when loaded presence pyrophosphate. SR membrane vesicles isolated normal pig were with...

Background/Aims: Alterations in intracellular Ca2+ concentration ([Ca2+]i) underlie the pathogenesis of various cardiovascular diseases. Caveolin-1 (Cav-1) is primary functional protein associated with caveolae, which are invaginations plasma membrane, and a regulator [Ca2+]i signaling. Caveolae Cav-1 increase activity store-operated channels (SOCC) rat pulmonary arterial smooth muscle cells (PASMCs), these enhancing effects were more pronounced rats hypertension (PH). Classical transient...

Pulmonary hypertension (PH) is characterized by enhanced vasoconstriction and vascular remodeling, which are attributable to the alteration of Ca²⁺ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). It well established that store-operated entry (SOCE) augmented PASMCs during PH it plays a crucial role development. Our previous studies showed melastatin-related transient receptor potential 8 (TRPM8) down-regulated animal models, activation TRPM8 causes relaxation...