Molecular mechanism of adaptation process of arterial chemoreceptor to hypoxic environments

动脉化学感受器适应缺氧环境过程的分子机制

• 批准号: 14570073
• 负责人: HAYASHIDA Yoshiaki
• 金额: $ 2.3万
• 依托单位: International Buddhist University Junior College Division (2003)University of Occupational and Environmental Health, Japan (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570073/
• 关键词: carotid body; chronic hypoxia; hypercapnia; adaptation; immunohistochemistry; autonomic nervous system; 頚動脈小体; 自立神経

Systemic hypoxia has been shown to produce different cardiovascular responses depending on arterial tension of carbon dioxide through central and peripheral chemoreceptors. This study was undertaken to examine the molecular mechanism of increases in size and number of glomus cells and vasculature of the rat carotid body, which has been exposed chronically to 10% hypoxia with 3 different tension of carbon dioxide (Hypocapnic hypoxia : Hypo, Isocapnic hypoxia : Iso and Hypercapnic hypoxia : Hyper). The results were as follows : 1) the carotid body increased several folds in size, when the duration of hypoxia lasted from 2 up to 12 weeks, but there was no difference in size of the carotid body between 8 and 12 weeks of hypoxia. This result suggested that 8 weeks are necessary time period for adaptation of the carotid body to hypoxia. 2) the abundance of neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreac … More tive nerve fibers was examined in rats chronically exposed to Hypo, Iso and Hyper, respectively. SP and CGRP decreased, but VP increased in all 3 of hypoxia. NPY did not change in Hypo and Iso, but increased in Hyper. When the abundance of neuropeptide-containing nerve fibers were examined in the carotid body exposed to Hypo for 2, 4, and 8 weeks, SP and CGRP increased transiently after 4 weeks and decreased after 8 weeks of Hypo. VIP increased in all periods of Hypo, and NPY was unchanged in the carotid bodies during Hypo. These results suggested that the neuropeptide-containing nerve fibers were involved in dilatation and/or contraction of blood vessels of the carotid body. 3)the carotid bodies without sinus nerve (sinus nerve denervation), the carotid body without both sinus nerve and sympathetic innervation, or the carotid body without both sinus nerve and sympatho-vagal innervation did not so increase in size in response to chronic Hypo as the intact one, but the carotid body without both sinus nerve and sympathetic innervation increased most in size among the three denervation groups. The result suggested that sinus nerve played a role in an incease in number and size of glomus cells and the vagus nerve did in control of the carotid body vasculature. 4) Hypercapnic normoxia (6% CO2) did neither produce an increase in size of the carotid body nor in number of glomus cells. Less

全身缺氧已被证明产生不同的心血管反应，这取决于通过中枢和外周化学感受器的二氧化碳动脉张力。本研究旨在探讨长期暴露于10%低氧和3种不同二氧化碳浓度（低碳酸缺氧：Hypo，等碳酸缺氧：Iso和高碳酸缺氧：Hyper）的大鼠颈动脉体血管小球细胞大小和数量增加的分子机制。结果表明：1)缺氧时间为2 ~ 12周时，颈动脉体的大小增加了数倍，但缺氧时间为8 ~ 12周时，颈动脉体的大小没有差异。提示8周是颈动脉体适应缺氧的必要时间。(2)长期暴露于Hypo、Iso和Hyper环境的大鼠神经纤维中，神经肽Y (NPY)-、血管活性肠多肽(VIP)-、P物质(SP)-和降钙素基因相关肽(CGRP)-免疫反应的丰度。低氧组SP、CGRP降低，VP升高。NPY在Hypo和Iso中没有变化，但在Hyper中增加。当检测暴露于Hypo 2、4和8周的颈动脉体中含有神经肽的神经纤维的丰富度时，SP和CGRP在4周后短暂升高，在Hypo 8周后下降。在hypoo的所有时期，VIP均升高，而在hypoo期间，颈动脉小体的NPY不变。这些结果提示含有神经肽的神经纤维参与了颈动脉体血管的扩张和/或收缩。3)无窦神经（窦神经去支配）、无窦神经和交感神经同时存在、无窦神经和交感迷走神经同时存在的颈动脉体在慢性Hypo作用下的体积增大不如完整的颈动脉体，但无窦神经和交感神经同时存在的颈动脉体在三种去支配组中体积增大最多。结果表明，窦神经在血管球细胞数量和大小的增加中起作用，迷走神经在颈动脉体血管的控制中起作用。4)高碳酸常氧（6% CO2）既不增加颈动脉体的大小，也不增加血管球细胞的数量。少

项目成果

Kusakabe T, Hirakawa H, Matsuda H, Yamamoto Y, Nagai T, Kawakami T, Takenaka T, Hayashida Y: "Changes in the peptidergic innovation in the carotid body of rats chronically exposed to hypercapnic hypoxia : an effect of arterial CO2 tension"Histology and Hi

Kusakabe T、Hirakawa H、Matsuda H、Yamamoto Y、Nagai T、Kawakami T、Takenaka T、Hayashida Y：“长期暴露于高碳酸血症缺氧的大鼠颈动脉体肽能创新的变化：动脉二氧化碳张力的影响”组织学

Kusakabe T, Matsuda H, Hayashida Y: "Rat carotid body in systemic hypoxia -Involvement of arterial CO2 tension in morphological changes."Adv Exp Med Biol. 536. 611-617 (2003)

Kusakabe T、Matsuda H、Hayashida Y：“全身缺氧的大鼠颈动脉体 - 动脉 CO2 张力参与形态变化。”Adv Exp Med Biol。

Hideki Matsuda: "Nitric oxide and calcium binding protein in hypoxic rat carotid body."Advances in Experimental Medicine and Biology. 536. 353-358 (2003)

松田秀树：“缺氧大鼠颈动脉体中的一氧化氮和钙结合蛋白。”实验医学和生物学进展。

Tatsumi Kusakabe: "Rat carotid bodies in systemic hypoxia-involvement of arterial CO2 tension in morphological changes."Advances in Experimental Medicine and Biology. 536. 611-617 (2003)

Tatsumi Kusakabe：“大鼠颈动脉体在全身缺氧中参与动脉二氧化碳张力的形态变化。”实验医学和生物学进展。

Hideki Matsuda: "Nitric oxide and calcium binding protein in hypoxic rat carotid body"Advances in Experimental Medicine and Biology. (in press). (2003)

松田秀树：“缺氧大鼠颈动脉体中的一氧化氮和钙结合蛋白”实验医学和生物学进展。