Salman Ibrahim M, Hildreth Cara M, Phillips Jacqueline K
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
Auton Neurosci. 2017 May;204:65-73. doi: 10.1016/j.autneu.2016.10.001. Epub 2016 Oct 11.
We investigated age- and sex-related changes in reflex renal sympathetic nerve activity (RSNA) and haemodynamic responses to vagal afferent stimulation in a rodent model of chronic kidney disease (CKD). Using anaesthetised juvenile (7-8weeks) and adult (12-13weeks) Lewis Polycystic Kidney (LPK) and Lewis control rats of either sex (n=63 total), reflex changes in RSNA, heart rate (HR) and mean arterial pressure (MAP) to vagal afferent stimulation (5-s train, 4.0V, 2.0-ms pulses, 1-16Hz) were measured. In all groups, stimulation of the vagal afferents below 16Hz produced frequency-dependent reductions in RSNA, HR and MAP, while a 16Hz stimulus produced an initial sympathoinhibition followed by sympathoexcitation. In juvenile LPK versus age-matched Lewis, sympathoinhibition was reduced when responses were expressed as % baseline (P<0.05), but not as microvolts, while bradycardic responses were greater. Reflex depressor responses were greater (P=0.015) only in juvenile female LPK. In adult LPK, reflex sympathoinhibition (%) was blunted (P<0.05), and an age-related decline apparent (when expressed as microvolts). Reflex reductions in HR and MAP were only diminished (P<0.05) in adult female LPK versus age-matched Lewis. Peak reflex sympathoexcitation at 16Hz did not differ between groups; however, area under the curve values were greater in the LPK versus Lewis (overall, 9±1 versus 19±3μVs, P<0.05) irrespective of age, suggestive of enhanced sympathoexcitatory drive in the LPK. Our data demonstrates a progressive deficit in the central processing of vagal afferent input and a differential sex influence on reflex regulation of autonomic function and blood pressure homeostasis in CKD.
我们在慢性肾脏病（CKD）啮齿动物模型中研究了反射性肾交感神经活动（RSNA）以及对迷走神经传入刺激的血流动力学反应的年龄和性别相关变化。使用麻醉的幼年（7 - 8周）和成年（12 - 13周）Lewis多囊肾（LPK）大鼠以及Lewis对照大鼠（雌雄皆有，共63只），测量了对迷走神经传入刺激（5秒串刺激，4.0V，2.0毫秒脉冲，1 - 16Hz）的RSNA、心率（HR）和平均动脉压（MAP）的反射性变化。在所有组中，低于16Hz的迷走神经传入刺激产生频率依赖性的RSNA、HR和MAP降低，而16Hz刺激产生初始的交感抑制，随后是交感兴奋。在幼年LPK大鼠与年龄匹配的Lewis大鼠相比时，以%基线表示反应时交感抑制降低（P<0.05），但以微伏表示时则不然，而心动过缓反应更大。仅在幼年雌性LPK大鼠中反射性降压反应更大（P = 0.015）。在成年LPK大鼠中，反射性交感抑制（%）减弱（P<0.05），且存在明显的年龄相关下降（以微伏表示时）。与年龄匹配的Lewis大鼠相比，仅成年雌性LPK大鼠的HR和MAP反射性降低（P<0.05）。16Hz时的峰值反射性交感兴奋在各组之间无差异；然而，LPK大鼠的曲线下面积值大于Lewis大鼠（总体上，9±1对19±3μVs，P<0.05），与年龄无关，提示LPK大鼠交感兴奋驱动增强。我们的数据表明，在CKD中，迷走神经传入输入的中枢处理存在渐进性缺陷，并且性别对自主功能和血压稳态的反射调节有不同影响。
