Institute of Clinical Pharmacology, Medical School Hannover, Hannover, Germany.
PLoS One. 2011;6(10):e25898. doi: 10.1371/journal.pone.0025898. Epub 2011 Oct 7.
Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects.
ClinicalTrials.gov NCT01237431.
水摄入会使人的交感神经活动急剧增加。在动物中，这种反应似乎是通过对渗透压敏感的肝脊髓传入神经上的瞬时受体电位通道 TRPV4 激活介导的，被描述为渗透压反应。我们假设肝去神经支配会减弱水摄入引起的交感神经激活。我们研究了 20 例肝移植受者（44±2.6 岁，移植后 1.2±0.1 年）作为肝去神经支配的模型，以及 20 例肾移植受者（43±2.6 岁，移植后 0.8±0.1 年）作为免疫抑制药物匹配的对照组。在摄入 500ml 水前后，我们采集静脉血样进行儿茶酚胺分析。我们还监测了肱动脉和手指血压、心电图和胸部生物阻抗。在 30-40 分钟的水摄入后，肝移植受者的血浆去甲肾上腺素浓度变化了 0.01±0.07 nmol/l，而肾移植受者的浓度变化了 0.21±0.07 nmol/l（两组之间有差异，p<0.05）。虽然两组的血压和全身血管阻力都增加了，但肝移植受者的反应倾向于减弱。我们的发现支持这样的观点，即渗透压敏感的肝传入神经参与了人类水摄入引起的交感神经激活。
ClinicalTrials.gov NCT01237431。
