Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
Am J Physiol Lung Cell Mol Physiol. 2011 Nov;301(5):L702-11. doi: 10.1152/ajplung.00128.2011. Epub 2011 Aug 5.
Chronic intermittent hypoxia (CIH), a characteristic of sleep obstructive apnea, enhances carotid body (CB) chemosensory responses to hypoxia, but its consequences on CB vascular area and VEGF expression are unknown. Accordingly, we studied the effect of CIH on CB volume, glomus cell numbers, blood vessel diameter and number, and VEGF immunoreactivity (VEGF-ir) in male Sprague-Dawley rats exposed to 5% O(2), 12 times/h for 8 h or sham condition for 21 days. We found that CIH did not modify the CB volume or the number of glomus cells but increased VEGF-ir and enlarged the vascular area by increasing the size of the blood vessels, whereas the number of the vessels was unchanged. Because oxidative stress plays an essential role in the CIH-induced carotid chemosensory potentiation, we tested whether antioxidant treatment with ascorbic acid may impede the vascular enlargement and the VEGF upregulation. Ascorbic acid, which prevents the CB chemosensory potentiation, failed to impede the vascular enlargement and the increased VEGF-ir. Thus present results suggest that the CB vascular enlargement induced by CIH is a direct effect of intermittent hypoxia and not secondary to the oxidative stress. Accordingly, the subsequent capillary changes may be secondary to the mechanisms involved in the neural chemosensory plasticity induced by intermittent hypoxia.
慢性间歇性低氧(CIH)是睡眠呼吸暂停的特征,增强颈动脉体(CB)对缺氧的化学敏感性反应,但它对 CB 血管面积和 VEGF 表达的影响尚不清楚。因此,我们研究了 CIH 对雄性 Sprague-Dawley 大鼠 CB 体积、球细胞数量、血管直径和数量以及 VEGF 免疫反应性(VEGF-ir)的影响,这些大鼠在 5%O2 下暴露 12 次/小时,持续 8 小时,或在 21 天内处于假处理条件下。我们发现,CIH 并未改变 CB 体积或球细胞数量,但增加了 VEGF-ir,并通过增大血管大小来增加血管面积,而血管数量没有变化。由于氧化应激在 CIH 诱导的颈动脉化学敏感性增强中起着至关重要的作用,我们测试了抗氧化剂抗坏血酸的治疗是否可能阻止血管扩大和 VEGF 的上调。抗坏血酸可预防 CB 化学敏感性增强,但不能阻止血管扩大和 VEGF-ir 的增加。因此,目前的结果表明,CIH 诱导的 CB 血管扩大是间歇性低氧的直接作用,而不是氧化应激的继发作用。因此,随后的毛细血管变化可能是由间歇性低氧诱导的神经化学敏感性可塑性所涉及的机制引起的。