Molecular mechanism of adaptation process of arterial chemoreceptor to hypoxic environments

已有研究表明，全身低氧通过中枢和外周化学感受器产生不同的心血管反应，这取决于动脉中二氧化碳的张力。本研究旨在探讨大鼠颈动脉小体在3种不同二氧化碳分压(低碳酸血症：Hypo、等碳酸血症：ISO和高碳酸血症：HYPER)下长期暴露于10%低氧条件下，血管球体和血管大小增加的分子机制。结果表明：1)低氧2~12周时，颈动脉小体增大数倍，8周和12周时颈动脉小体大小无明显差异。提示8周是颈动脉小体对低氧适应的必要时间段。2)神经肽Y、血管活性肠多肽、P物质和降钙素基因相关肽免疫反应…的含量在慢性暴露于Hypo、Iso和Hyper的大鼠中，检测到了更多的运动性神经纤维。低氧3组SP、CGRP均降低，VP升高。Hypo和Iso组NPY无明显变化，Hyper组NPY升高。低氧暴露2、4、8周后，颈动脉小体内神经肽类神经纤维含量增加，4周后SP和CGRP一过性升高，8周后降低。VIP在Hypo各时期均升高，颈动脉小体NPY在Hypo期间无明显变化。这些结果提示，神经肽类神经纤维参与了颈动脉小体血管的扩张和/或收缩。3)无窦神经支配(窦神经支配)的颈动脉小体、无窦神经和交感神经支配的颈动脉小体、无窦神经和交感迷走神经支配的颈动脉小体对慢性缺氧的反应不如正常颈动脉小体大，但无窦神经和交感神经支配的颈动脉小体体积增大最大。结果提示，窦神经参与了颈动脉球体细胞数量和大小的增加，迷走神经参与了颈动脉小体血管的调控。4)高二氧化碳常氧(6%CO2)既不增加颈动脉小体的大小，也不增加球体细胞的数量。较少

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