Lam Siu Yin, Leung Po Sing
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, PR China.
Regul Pept. 2002 Jul 15;107(1-3):97-103. doi: 10.1016/s0167-0115(02)00068-x.
Previous studies have shown the existence of functional angiotensin II receptors in rat carotid body, which directly alters the carotid chemoreceptor afferent nerve activity. Moreover, chronic hypoxia could result in an enhanced sensitivity of chemoreceptor afferent activity via an AT(1) receptor-mediated calcium signaling in the carotid body. In the present study, the localization and expression of angiotensinogen, the obligatory component for an intrinsic, angiotensin-generating system, were investigated by in situ hybridization histochemistry, immunohistochemistry, RT-PCR, Western blot and Northern blot analysis. In situ hybridization showed the expression of angiotensinogen within the glomus cells of the carotid body. Double immunostaining of angiotensinogen and tyrosine hydroxylase, an immunohistochemical marker for type I glomus cells, elucidated that angiotensinogen protein was specifically localized to the lobules of type I cells. Consistently, RT-PCR and Western blot analysis confirmed the expression of angiotensinogen mRNA and protein, respectively. On the other hand, renin mRNA was not detected using RT-PCR and Northern blot analysis whereas angiotensin-converting enzyme (ACE) mRNA was detected in the carotid body. These data suggest that a locally generated angiotensin system is operated in the carotid body, which might be linked to a renin-independent biosynthetic pathway. Such an intrinsic, angiotensin-generating system and its local regulation by chronic hypoxia should be important in the modulation of cardiopulmonary adaptation in the hypoxic ventilatory response and the electrolyte as well as water homeostasis.
先前的研究表明，大鼠颈动脉体中存在功能性血管紧张素II受体，其可直接改变颈动脉化学感受器传入神经活动。此外，慢性缺氧可通过颈动脉体中AT(1)受体介导的钙信号传导导致化学感受器传入活动的敏感性增强。在本研究中，通过原位杂交组织化学、免疫组织化学、逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和Northern印迹分析，对血管紧张素原（一种内在的血管紧张素生成系统的必需成分）的定位和表达进行了研究。原位杂交显示颈动脉体的球细胞内有血管紧张素原的表达。血管紧张素原与酪氨酸羟化酶（I型球细胞的免疫组织化学标志物）的双重免疫染色表明，血管紧张素原蛋白特异性定位于I型细胞的小叶。同样，RT-PCR和蛋白质免疫印迹分析分别证实了血管紧张素原mRNA和蛋白的表达。另一方面，使用RT-PCR和Northern印迹分析未检测到肾素mRNA，而在颈动脉体中检测到了血管紧张素转换酶（ACE）mRNA。这些数据表明，颈动脉体中存在一个局部生成的血管紧张素系统，其可能与一条不依赖肾素的生物合成途径有关。这样一个内在的血管紧张素生成系统及其受慢性缺氧的局部调节，在低氧通气反应中对心肺适应的调节以及电解质和水平衡方面应该具有重要意义。
