Saha Manash, Menuet Clement, Sun Qi-Jian, Burke Peter G R, Hildreth Cara M, Allen Andrew M, Phillips Jacqueline K
Department of Biomedical Sciences, Macquarie University, Australia; Department of Nephrology, National Institute of Kidney Disease and Urology, Bangladesh; Graduate School of Medicine, Wollongong University, Australia; Department of Medicine, Wollongong Hospital, Australia.
Department of Physiology, University of Melbourne, Australia; Institut de Neurobiologie de la Méditerranée, INMED UMR1249, INSERM, Aix-Marseille Université, Marseille, France.
Respir Physiol Neurobiol. 2019 Apr;262:57-66. doi: 10.1016/j.resp.2019.02.001. Epub 2019 Feb 2.
Respiratory modulation of sympathetic nerve activity (respSNA) was studied in a hypertensive rodent model of chronic kidney disease (CKD) using Lewis Polycystic Kidney (LPK) rats and Lewis controls. In adult animals under in vivo anaesthetised conditions (n = 8-10/strain), respiratory modulation of splanchnic and renal nerve activity was compared under control conditions, and during peripheral (hypoxia), and central, chemoreceptor (hypercapnia) challenge. RespSNA was increased in the LPK vs. Lewis (area under curve (AUC) splanchnic and renal: 8.7 ± 1.1 vs. 3.5 ± 0.5 and 10.6 ± 1.1 vs. 7.1 ± 0.2 μV.s, respectively, P < 0.05). Hypoxia and hypercapnia increased respSNA in both strains but the magnitude of the response was greater in LPK, particularly in response to hypoxia. In juvenile animals studied using a working heart brainstem preparation (n = 7-10/strain), increased respSNA was evident in the LPK (thoracic SNA, AUC: 0.86 ± 0.1 vs. 0.42 ± 0.1 μV.s, P < 0.05), and activation of peripheral chemoreceptors (NaCN) again drove a larger increase in respSNA in the LPK with no difference in the response to hypercapnia. Amplified respSNA occurs in CKD and may contribute to the development of hypertension.
利用刘易斯多囊肾(LPK)大鼠和刘易斯对照大鼠,在慢性肾病(CKD)的高血压啮齿动物模型中研究了交感神经活动的呼吸调制(respSNA)。在体内麻醉条件下的成年动物(每组n = 8 - 10只)中,比较了在对照条件下、外周(低氧)和中枢化学感受器(高碳酸血症)刺激期间内脏和肾神经活动的呼吸调制。与刘易斯大鼠相比,LPK大鼠的respSNA增加(内脏和肾的曲线下面积(AUC):分别为8.7±1.1与3.5±0.5以及10.6±1.1与7.1±0.2 μV·s,P < 0.05)。低氧和高碳酸血症均增加了两种品系的respSNA,但LPK大鼠的反应幅度更大,尤其是对低氧的反应。在使用工作心脏脑干标本研究的幼年动物中(每组n = 7 - 10只),LPK大鼠中明显存在respSNA增加(胸段SNA,AUC:0.86±0.1与0.42±0.1 μV·s,P < 0.05),并且外周化学感受器激活(NaCN)再次使LPK大鼠的respSNA有更大增加,而对高碳酸血症的反应无差异。CKD中会出现增强的respSNA,这可能导致高血压的发生。