Department of Biomedical Sciences, University of Missouri, Columbia, Missouri 65211, USA.
Am J Physiol Regul Integr Comp Physiol. 2012 May 15;302(10):R1219-32. doi: 10.1152/ajpregu.00028.2012. Epub 2012 Mar 7.
Peripheral chemoreceptor afferent information is sent to the nucleus tractus solitarii (nTS), integrated, and relayed to other brain regions to alter cardiorespiratory function. The nTS projects to the hypothalamic paraventricular nucleus (PVN), but activation and phenotype of these projections during chemoreflex stimulation is unknown. We hypothesized that activation of PVN-projecting nTS neurons occurs primarily at high intensities of hypoxia. We assessed ventilation and cardiovascular parameters in response to increasing severities of hypoxia. Retrograde tracers were used to label nTS PVN-projecting neurons and, in some rats, rostral ventrolateral medulla (RVLM)-projecting neurons. Immunohistochemistry was performed to identify nTS cells that were activated (Fos-immunoreactive, Fos-IR), catecholaminergic, and GABAergic following hypoxia. Conscious rats underwent 3 h normoxia (n = 4, 21% O(2)) or acute hypoxia (12, 10, or 8% O(2); n = 5 each). Hypoxia increased ventilation and the number of Fos-IR nTS cells (21%, 13 ± 2; 12%, 58 ± 4; 10%, 166 ± 22; 8%, 186 ± 6). Fos expression after 10% O(2) was similar whether arterial pressure was allowed to decrease (-13 ± 1 mmHg) or was held constant. The percentage of PVN-projecting cells activated was intensity dependent, but contrary to our hypothesis, PVN-projecting nTS cells exhibiting Fos-IR were found at all hypoxic intensities. Notably, at all intensities of hypoxia, ∼75% of the activated PVN-projecting nTS neurons were catecholaminergic. Compared with RVLM-projecting cells, a greater percentage of PVN-projecting nTS cells was activated by 10% O(2). Data suggest that increasing hypoxic intensity activates nTS PVN-projecting cells, especially catecholaminergic, PVN-projecting neurons. The nTS to PVN catecholaminergic pathway may be critical even at lower levels of chemoreflex activation and more important to cardiorespiratory responses than previously considered.
外周化学感受器传入信息被发送到孤束核（nTS），在那里整合并中继到其他脑区以改变心肺功能。nTS 投射到下丘脑室旁核（PVN），但在化学反射刺激期间这些投射的激活和表型尚不清楚。我们假设，在缺氧强度较高时，PVN 投射 nTS 神经元的激活主要发生。我们评估了对缺氧严重程度增加的通气和心血管参数的反应。逆行示踪剂用于标记 nTS-PVN 投射神经元，在一些大鼠中，标记延髓头端腹外侧区（RVLM）投射神经元。免疫组织化学用于鉴定在缺氧后被激活（Fos-免疫反应性，Fos-IR）、儿茶酚胺能和 GABA 能的 nTS 细胞。清醒大鼠经历 3 小时的常氧（n = 4，21%O2）或急性缺氧（12、10 或 8%O2；n = 5 只）。缺氧增加通气和 Fos-IR nTS 细胞的数量（21%，13 ± 2；12%，58 ± 4；10%，166 ± 22；8%，186 ± 6）。在 10%O2 下，动脉压允许下降（-13 ± 1 mmHg）或保持不变时，Fos 表达相似。激活的 PVN 投射细胞的百分比与强度有关，但与我们的假设相反，在所有缺氧强度下都发现了表现出 Fos-IR 的 PVN 投射 nTS 细胞。值得注意的是，在所有缺氧强度下，约 75%的激活的 PVN 投射 nTS 神经元是儿茶酚胺能的。与 RVLM 投射细胞相比，更多百分比的 PVN 投射 nTS 细胞被 10%O2 激活。数据表明，增加缺氧强度会激活 nTS-PVN 投射细胞，特别是儿茶酚胺能、PVN 投射神经元。即使在较低的化学反射激活水平下，nTS 到 PVN 的儿茶酚胺能通路也可能至关重要，并且比以前认为的对心肺反应更为重要。
