Chronic hypoxia upregulates adenosine 2a receptor expression in chromaffin cells via hypoxia inducible factor-2α: role in modulating secretion. | LitMetric
Catecholamine (CAT) release from chromaffin tissue plays an essential role in the fetus which develops in a low O₂ environment (hypoxia). To address molecular mechanisms regulating CAT secretion in low O₂, we exposed a fetal chromaffin-derived cell line (MAH cells) to chronic hypoxia (CHox; 2% O₂, 24h) and assessed gene expression using microarrays, quantitative RT-PCR, and western blot. CHox caused a dramatic ∼12× upregulation of adenosine A2a receptor (A2aR) mRNA, an effect critically dependent upon hypoxia-inducible factor (HIF)-2α which bound the promoter of the A2aR gene. In amperometric studies, acute hypoxia and high K⁺ (30 mM) evoked quantal CAT secretion that was enhanced after CHox, and further potentiated during simultaneous A2aR activation by adenosine. A2aR activation also enhanced stimulus-induced rise in intracellular Ca²⁺ in control, but not HIF-2α-deficient, MAH cells. Thus, A2aR, adenosine, and HIF-2α are key contributors to the potentiation of CAT secretion in developing chromaffin cells during chronic hypoxia.
Lance Adams syndrome (LAS) is characterized by chronic action or intention myoclonus resulting from cerebral hypoxia. Perampanel, a non-competitive antagonist of aamino-3-hydroxy-5methyl-4 isooxazoleproprionic acid glutamate receptor, has demonstrated some efficacy in myoclonic epilepsy and other types of myoclonus. We report significant benefit in a patient with LAS treated with add on perampanel and provide a review of the relevant literature.
Background: Chronic arterial hypertension restructures the vascular architecture of the brain, leading to a series of pathological responses that culminate in cerebral small-vessel disease. Pericytes respond dynamically to vascular challenges; however, how they manifest under the continuous strain of hypertension has not been elucidated.
Methods And Results: In this study, we characterized pericyte behavior alongside hypertensive states in the spontaneously hypertensive stroke-prone rat model, focusing on their phenotypic and metabolic transformation.
Innovative advancements in preclinical imaging have led to the development of cone-beam computed tomography (CBCT) combined with contrast free pulmonary angiography (CFPA), a novel lung scanning technology capable of assessing lung function and pulmonary vascular morphology. This cutting-edge approach integrates CBCT to provide detailed quantification of the pulmonary vascular tree. The application of this technique to image and quantify changes in the pulmonary vascular tree of mice exposed to chronic hypoxia has not been investigated.
Obstructive sleep apnea (OSA) is a state of sleep disorder, characterized by repetitive episodes of apnea and chronic intermittent hypoxia. OSA has an extremely high prevalence worldwide and represents a serious challenge to public health, yet its severity is frequently underestimated. It is now well established that neurocognitive dysfunction, manifested as deficits in attention, memory, and executive functions, is a common complication observed in patients with OSA, whereas the specific pathogenesis remains poorly understood, despite the likelihood of involvement of inflammation.
Clinical Department of National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, People's Republic of China.
Purpose: Chronic intermittent hypoxia (CIH) is considered one of the main pathophysiological mechanisms of obstructive sleep apnea (OSA). CIH can further lead to cognitive dysfunction by inducing processes such as neuroinflammation and oxidative stress. The hippocampus is primarily associated with cognitive functions such as learning and memory.
