Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
Neuropeptides. 2018 Feb;67:87-94. doi: 10.1016/j.npep.2017.11.006. Epub 2017 Nov 8.
Delivery of neuropeptide Y (NPY) to the brain by intranasal administration shows promise as non-invasive means for preventing or treating PTSD symptoms. Here, radiotelemetry and echocardiography were used to determine effects of intranasal NPY on cardiovascular functions in absence and presence of stress. Male adult Sprague Dawley rats were implanted with radiotelemetric probes, and subjected to single prolonged stress (SPS), followed by intranasal vehicle (V) or NPY (150μg) under conditions shown to prevent development of many of the behavioral neuroendocrine and biochemical impairments. In both groups, mean arterial pressure (MAP) rose rapidly peaking at about 125mmHg, remaining near maximal levels for 1h. SPS also elicited robust rise in heart rate (HR) which was mitigated by intranasal NPY, and significantly lower than V-treated rats 12-50min after exposure to SPS stressors. In the first hr. after SPS, locomotor activity was elevated but only in the V-treated group. By 3h, MAP returned to pre-stress levels in both groups with no further change when monitored for 6days. HR remained elevated during the 6h remaining light phase after SPS. Subsequently HR was at pre-SPS levels during the remaining days. However dark phase HR was low following SPS, gradually recovered over 6days and was associated with reduced activity. When administered in the absence of further stress, intranasal NPY or V elicited similar much smaller, short-lived rises in MAP and HR. Echocardiography revealed no change in HR, stroke volume (SV) or cardiac output (Q) with intranasal NPY in the absence of stress. SPS led to reduced SV and Q but was not affected by NPY. Overall the results demonstrate no major cardiovascular effects of intranasal NPY and indicate possible benefit from transient amelioration of HR response in line with its translational potential to combat PTSD and comorbid impairments.
经鼻给予神经肽 Y（NPY）到大脑显示出作为预防或治疗 PTSD 症状的非侵入性手段的希望。在这里，使用无线电遥测和超声心动图来确定经鼻 NPY 对心血管功能的影响，无论是在没有压力的情况下还是在存在压力的情况下。雄性成年 Sprague Dawley 大鼠被植入无线电遥测探头，并在已被证明可预防许多行为神经内分泌和生化损伤发展的条件下，接受单次延长压力（SPS），然后接受鼻腔载体（V）或 NPY（150μg）。在这两组中，平均动脉压（MAP）迅速升高，峰值约为 125mmHg，持续近最大水平 1 小时。SPS 还引起心率（HR）的剧烈升高，经鼻 NPY 减轻了这种升高，并且在暴露于 SPS 应激源后 12-50 分钟，显著低于 V 处理的大鼠。在 SPS 后的第一个小时内，运动活性升高，但仅在 V 处理的组中升高。到 3 小时时，两组的 MAP 均恢复到应激前水平，在监测 6 天期间没有进一步变化。SPS 后剩余的 6 小时光照相期间，HR 仍然升高。随后，HR 在剩余的日子里恢复到 SPS 前的水平。然而，SPS 后暗相 HR 较低，逐渐在 6 天内恢复，活动减少。当在没有进一步压力的情况下给药时，经鼻 NPY 或 V 引起的 MAP 和 HR 的相似的、短暂的升高要小得多。超声心动图显示，在没有压力的情况下，经鼻 NPY 对 HR、每搏量（SV）或心输出量（Q）没有影响。SPS 导致 SV 和 Q 降低，但不受 NPY 影响。总的来说，这些结果表明经鼻 NPY 对心血管系统没有重大影响，并表明在其翻译潜力对抗 PTSD 和共病损伤方面，短暂改善 HR 反应可能具有益处。
