Molecular mechanism of adaptation process of arterial chemoreceptor to hypoxic environments

全身性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。本研究旨在研究大鼠颈动脉体血管球细胞和血管系统的大小和数量增加的分子机制，大鼠颈动脉体长期暴露于10%缺氧和3种不同二氧化碳浓度（低碳酸血症缺氧：Hypo，等碳酸血症缺氧：Iso和高碳酸血症缺氧：Hyper）。结果表明：（1）缺氧2 ~ 12周时，颈动脉体增大数倍，而缺氧8 ~ 12周时，颈动脉体大小无明显变化;提示8周是颈动脉体适应缺氧的必要时间。2)神经肽Y（NPY）、血管活性肠肽（VIP）、P物质（SP）和降钙素基因相关肽（CGRP）免疫反应物丰度 ...更多信息 分别对慢性暴露于Hypo、Iso和Hyper的大鼠进行了神经纤维检查。3种缺氧状态下SP、CGRP均降低，VP均升高。Hypo和Iso时NPY无变化，Hyper时增加。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度时，SP和CGRP在Hypo 4周后短暂升高，在Hypo 8周后降低。VIP在Hypo各时段均升高，而NPY在Hypo时颈动脉体中无变化。这些结果表明，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（去窦神经）、既无窦神经又无交感神经支配的颈动脉体、既无窦神经又无交感-迷走神经支配的颈动脉体对慢性Hypo的反应没有完整的颈动脉体那么大，但在三个去神经组中，既无窦神经又无交感神经支配的颈动脉体的大小增加最多。结果提示，窦神经对颈动脉球细胞的数量和体积的增加起一定作用，迷走神经对颈动脉体血管系统起一定的控制作用。4)高碳酸正常氧（6%CO2）既没有产生颈动脉体的大小也没有增加血管球细胞的数量。少

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