CHRONIC HYPOXIA EFFECTS ON CAROTID CHEMORECEPTION

描述（申请人摘要）：哺乳动物颈动脉体，一种动脉 化学感觉器官，由专门的化学感觉I型细胞组成 和支持性II型细胞，它们嵌在密集的有孔网状结构中， 毛细血管和血窦。 响应于自然刺激（例如，缺氧， 高碳酸血症）时，I型细胞释放多种神经递质剂， 兴奋颈动脉窦神经的化学传入神经末梢。 的 颈动脉体是动脉血中溶解O2的主要传感器， 因此，它对于发生在动物体内的 在长时间暴露于高海拔地区，以及在各种其他 涉及急性和慢性低氧血症的生理和病理状态。 作为对慢性缺氧（CH）的反应，颈动脉体经历了显著的 形态学改变，包括I型肥大和增生 细胞和血管体积的急剧增加（新血管形成）。 此外，对缺氧的化学敏感性逐渐增加。 事实上，人们对介导这种疾病的细胞机制一无所知。 这些变化。 根据我们的初步数据，我们假设四个 物质，所有内源性的颈动脉体，密切参与， 组织重塑和重塑以及增加的 化学敏感性，这发生在CH。这些物质是血管 内皮生长因子（VEGF），内皮素（ET），心钠素 肽（ANP）和一氧化氮（NO）。 它们有共同的血管， 促有丝分裂和神经调节特性。 利用分子生物学， 免疫细胞化学、电生理学和神经化学技术， 拟议的研究将探讨：一。CH对细胞凋亡的影响 这四种物质及其在颈动脉体中的受体; II. 他们的 在CH颈动脉体中的组织生长和组织重塑中的作用; III. 它们的上调和对改变化疗敏感性的贡献， 然后是CH;和IV。 CH对细胞信号传导机制的影响 通过VEGF、ET、ANP和NO介导。

DESCRIPTION (Applicant's abstract): The mammalian carotid body, an arterial chemosensory organ, is comprised of specialized chemosensory type I cells and supportive type II cells embedded in a dense network of fenestrated capillaries and sinusoids. In response to natural stimuli (e.g., hypoxia, hypercapnia), type I cells release multiple neurotransmitter agents which excite chemoafferent nerve terminals of the carotid sinus nerve. The carotid body is the primary sensor for dissolved O2 in arterial blood, and as such, it is essential for the ventilatory acclimatization, which occurs during prolonged exposure to high altitude, and in a variety of other physiological and pathological states involving acute and chronic hypoxemia. In response to chronic hypoxia (CH), the carotid body undergoes remarkable morphological changes, including hypertrophy and hyperplasia of type I cells, and a dramatic increase in blood vessel volume (neo-vascularization). In addition, there is a gradual increase in chemosensitivity to hypoxia. Virtually nothing is known about the cellular mechanisms, which mediate these changes. Based upon our preliminary data, we hypothesize that four substances, all endogenous to the carotid body, are intimately involved in the tissue remodeling and reshaping as well as the increased chemosensitivity, which occurs during CH. These substances are vascular endothelial growth factor (VEGF), endothelin (ET), atrial natriuretic peptide (ANP) and nitric oxide (NO). They have in common vascular, mitogenic and neuro-regulatory properties. Using molecular biological, immunocytochemical, electrophysiological and neurochemical techniques, our proposed studies will explore: I. The effects of CH on the expression of these four substances and their receptors in the carotid body; II. Their role in tissue growth and tissue remodeling in the CH carotid body; III. Their up-regulation and contribution to the altered chemosensitivity which follows CH; and IV. The effects of CH on the cellular signaling mechanisms mediated by VEGF, ET, ANP and NO in this chemoreceptive tissue.