Chronic intermittent hypoxia-induced augmented cardiorespiratory outflow mediated by vasopressin-V₁A receptor signaling in the medulla.
Chronic intermittent hypoxia-induced augmented cardiorespiratory outflow mediated by vasopressin-V₁A receptor signaling in the medulla.
复制标题
髓质中加压素-VαA 受体信号介导的慢性间歇性缺氧引起的心肺流出量增加。
DOI：
10.1007/978-1-4419-7756-4_43
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发表时间：
2011
影响因子：
--
通讯作者：
Dick,ThomasE
中科院分区：
文献类型：
--
作者：
Prabha,Kc;Balan,KannanV;Martin,RichardJ;Lamanna,JosephC;Haxhiu,MusaA;Dick,ThomasE
睡眠呼吸障碍的共同发病是高血压合并交感神经活性升高，这可能是慢性间歇性低氧(CIH)引起的。脑出血引起心肺调节部位的可塑性，包括室旁核(PVN)，其作用是维持交感神经活动的增加。我们的工作假设是，加压素神经元介导了与脑出血相关的血压持续升高和呼吸改变。在一系列神经解剖学实验中，我们确定了含有加压素的PVN神经元是否支配延髓头端腹外侧区(RVLM)，而CIH(每天8小时，连续10天)引起的心肺反应的改变是由延髓中的加压素-V1A受体信号介导的。在第一组实验中，霍乱毒素β亚单位被微量注射到视网膜室旁核，以描绘室旁核的神经支配。免疫组织化学结果显示，含有加压素的下丘脑室旁核神经元与霍乱毒素β亚单位双标，表明加压素投射到腹侧腹侧背侧核。在第二组中，对延髓切片进行血管加压素V1a受体的免疫标记，其在脑出血大鼠的RVLM和邻近的吻侧腹侧呼吸柱的表达明显高于RAH-大鼠。在一系列生理学实验中，我们确定阻断延髓中的加压素V1A受体是否能使脑缺血大鼠的血压恢复正常，并减弱对PVN去抑制的诱发反应。在麻醉、呼吸和迷走神经切断的大鼠中记录血压、心率、横隔肌和膝舌肌的活动。在阻断后叶加压素V1a受体前后，微量注射荷包牡丹碱可解除PVN的抑制作用。在RA状态的大鼠，去抑制PVN增加血压、心率、微小的横隔肌和膝舌肌的活动，这些增加在阻断血管加压素V1a受体后被减弱。在CIH条件下的大鼠中，需要更大剂量的阻滞剂来钝化这些生理反应，并使基线血压正常化。我们的发现表明，加压素是从PVN神经元释放的神经肽，通过RVLM和头端腹侧呼吸柱调节心肺输出。
A co-morbidity of sleep-disordered breathing is hypertension associated with elevated sympathetic nerve activity, which may result fromchronic intermittent hypoxia (CIH). CIH evokes plasticity in cardiorespiratory regulating sites, including the paraventricular nucleus (PVN), which acts to sustain increased sympathetic nerve activity. Our working hypothesis is that vasopressin neurons mediate the sustained increase in blood pressure and altered breathing associated with CIH. In a series of neuroanatomical experiments, we determined if vasopressin-containing PVN neurons innervate rostral ventrolateral medulla (RVLM), and altered cardiorespiratory responses induced by CIH conditioning (8h/day for 10 days) is mediated by vasopressin-V1Areceptor signaling in the medulla. In the first set of experiments, cholera toxinβsubunit was microinjected into the RVLM to delineate innervation of the PVN. Immunohistochemistry data showed vasopressin-containing PVN neurons were double-labeled with cholera toxinβsubunit, indicating vasopressin projection to the RVLM. In the second set, sections of the medulla were immunolabeled for vasopressin V1Areceptor, and its expression was significantly higher in the RVLM and in the neighboring rostral ventral respiratory column in CIH- than from RAconditioned rats. In a series of physiological experiments,we determined if blocking the vasopressin V1Areceptor in the medulla would normalize blood pressure in CIHconditioned rats and also attenuate the evoked responses to PVN disinhibition.Blood pressure, heart rate, diaphragmatic and genioglossus muscle activity were recorded in anesthetized, ventilated and vagotomized rats. The PVN was disinhibited by microinjecting bicuculline before and after blocking vasopressin V1Areceptors in the RVLM/rostral ventral respiratory column. In RA-conditioned rats, PVN disinhibition increased blood pressure, heart rate, minute diaphragmatic and genioglossus muscle activity, and these increases were attenuated after blocking the vasopressin V1Areceptor. In CIH-conditioned rats, a significantly greater dose of blocker was required to blunt these physiological responses and it also normalized the baseline blood pressure. Our findings indicate that vasopressin is the neuropeptide released from PVN neurons that modulates cardiorespiratory output via the RVLMand rostral ventral respiratory column.