δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity.
δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity.
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DOI：
10.1016/j.autneu.2016.07.007
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发表时间：
2016-07
影响因子：
2.7
通讯作者：
Caffrey, James L.
中科院分区：
文献类型：
--
作者：
Estrada, Juan A.;Barlow, Mathew A.;Yoshishige, Darice;Williams, Arthur G., Jr.;Downey, H. Fred;Mallet, Robert T.;Caffrey, James L.
间歇性低氧训练(IHT)对缺血-再灌注性心肌梗死和心律失常有较强的心肌保护作用。通过拮抗β1肾上腺素能或δ阿片受体(δ-OR)阻断这种心脏保护，提示自主神经和/或阿片能适应。为了验证IHT使心脏自主神经平衡向更大的胆碱能和阿片能影响方向移动的假设。用δ-OR拮抗剂纳曲哚(200μg/kg sc)进行20d间歇、非缺氧性假训练或间歇性低氧训练。观察δ-OR激动剂甲硫氨酸脑啡肽-精氨酸-苯丙氨酸经窦房微透析给药后的迷走神经松解作用。分析δ-OR、神经营养单唾液神经节苷脂、GM-1以及胆碱能和肾上腺素能标志物的变化。与假手术组相比，间歇性高血压可增强迷走性心动过缓(P<；0.05)，并减弱甲硫氨酸脑啡肽-精氨酸-苯丙氨酸的δ_2-OR介导的迷走神经溶解作用。GM-1标记纤维与胆碱能标记物强烈重叠，间歇性羟色胺使这两种信号的强度增加(P<；0.05)。IHT增加了窦房结纤维的低和高强度囊泡性乙酰胆碱转运体标记(P<；0.05)，提示副交感神经分支增加。与上述迷走神经溶解δ-OR信号的缓和一致，间歇性高血压减少了心房和窦房结中的精选δ-OR标记纤维(P<；0.05)。此外，与假手术组和未治疗组相比，纳曲吲哚阻断δ-OR信号通路可增加δ-OR(房室)和囊泡乙酰胆碱转运体(房室)的蛋白含量。IHT还降低了交感神经标志物--脑室酪氨酸羟化酶(P<；0.05)。IHT通过阿片能、神经节苷脂和肾上腺素能系统的适应改变心脏自主神经平衡，有利于副交感神经控制。
Intermittent hypoxia training (IHT) produces robust myocardial protection against ischemia-reperfusion induced infarction and arrhythmias. Blockade of this cardioprotection by antagonism of either β1-adrenergic or δ-opioid receptors (δ-OR) suggests autonomic and/or opioidergic adaptations. To test the hypothesis that IHT shifts cardiac autonomic balance toward greater cholinergic and opioidergic influence. Mongrel dogs completed 20 d IHT, non-hypoxic sham training, or IHT with the δ-OR antagonist naltrindole (200 μg/kg sc). The vagolytic effect of the δ-OR agonist met-enkephalin-arg-phe delivered by sinoatrial microdialysis was evaluated following IHT. Sinoatrial, atrial and left ventricular biopsies were analyzed for changes in δ-OR, the neurotrophic monosialoganglioside, GM-1, and cholinergic and adrenergic markers. IHT enhanced vagal bradycardia vs. sham dogs (P<0.05), and blunted the δ2-OR mediated vagolytic effect of met-enkephalin-arg-phe. The GM- 1 labeled fibers overlapped strongly with cholinergic markers, and IHT increased the intensity of both signals (P<0.05). IHT increased low and high intensity vesicular acetylcholine transporter labeling of sinoatrial nodal fibers (P<0.05) suggesting an increase in parasympathetic arborization. IHT reduced select δ-OR labeled fibers in both the atria and sinoatrial node (P<0.05) consistent with moderation of the vagolytic δ2-OR signaling described above. Furthermore, blockade of δ-OR signaling with naltrindole during IHT increased the protein content of δ-OR (atria and ventricle) and vesicular acetylcholine transporter (atria) vs. sham and untreated IHT groups. IHT also reduced the sympathetic marker, tyrosine hydroxylase in ventricle (P<0.05). IHT shifts cardiac autonomic balance in favor of parasympathetic control via adaptations in opioidergic, ganglioside, and adrenergic systems.
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影响因子：
9.5
作者：
Estrada, Juan A.;Williams, Arthur G., Jr.;Mallet, Robert T.
通讯作者：
Mallet, Robert T.
影响因子：
4.7
作者：
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影响因子：
3.2
作者：
Deo, Shekhar H.;Barlow, Matthew A.;Caffrey, James L.
通讯作者：
Caffrey, James L.
影响因子：
3.2
作者：
Zong, P;Setty, S;Downey, HF
通讯作者：
Downey, HF
影响因子：
2.5
作者：
Mousa, Shaaban A.;Shaqura, Mohammed;Abdul-Khaliq, Hashim
通讯作者：
Abdul-Khaliq, Hashim