Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia;
Am J Physiol Regul Integr Comp Physiol. 2014 Apr 15;306(8):R567-75. doi: 10.1152/ajpregu.00460.2013. Epub 2014 Feb 12.
Hypertonic NaCl infused into the carotid arteries increases mean arterial pressure (MAP) and changes sympathetic nerve activity (SNA) via cerebral mechanisms. We hypothesized that elevated sodium levels in the blood supply to the brain would induce differential responses in renal and cardiac SNA via sensors located outside the blood-brain barrier. To investigate this hypothesis, we measured renal and cardiac SNA simultaneously in conscious sheep during intracarotid infusions of NaCl (1.2 M), sorbitol (2.4 M), or urea (2.4 M) at 1 ml/min for 4 min into each carotid. Intracarotid NaCl significantly increased MAP (91 ± 2 to 97 ± 3 mmHg, P < 0.05) without changing heart rate (HR). Intracarotid NaCl was associated with no change in cardiac SNA (11 ± 5.0%), but a significant inhibition of renal SNA (-32.5 ± 6.4%, P < 0.05). Neither intracarotid sorbitol nor urea changed MAP, HR, central venous pressure, cardiac SNA, and renal SNA. The changes in MAP and renal SNA were completely abolished by microinjection of the GABA agonist muscimol (5 mM, 500 nl each side) into the paraventricular nucleus of the hypothalamus (PVN). Infusion of intracarotid NaCl for 20 min stimulated a larger increase in water intake (1,100 ± 75 ml) than intracarotid sorbitol (683 ± 125 ml) or intracarotid urea (0 ml). These results demonstrate that acute increases in blood sodium levels cause a decrease in renal SNA, but no change in cardiac SNA in conscious sheep. These effects are mediated by cerebral sensors located outside the blood-brain barrier that are more responsive to changes in sodium concentration than osmolality. The renal sympathoinhibitory effects of sodium are mediated via a pathway that synapses in the PVN.
高渗氯化钠注入颈动脉会增加平均动脉压（MAP），并通过大脑机制改变交感神经活动（SNA）。我们假设，大脑血液供应中钠离子水平的升高会通过位于血脑屏障外的传感器，引起肾脏和心脏 SNA 的不同反应。为了验证这一假设，我们在清醒绵羊中同时测量了颈动脉内输注 1.2 M 氯化钠（NaCl）、2.4 M 山梨醇（sorbitol）或 2.4 M 尿素（urea）4 分钟时的肾和心 SNA，流速为 1ml/min。颈动脉内 NaCl 显著升高 MAP（91±2 至 97±3mmHg，P<0.05），而不改变心率（HR）。颈动脉内 NaCl 与心脏 SNA 无变化（11±5.0%）相关，但显著抑制肾 SNA（-32.5±6.4%，P<0.05）。颈动脉内山梨醇或尿素均不改变 MAP、HR、中心静脉压、心脏 SNA 和肾 SNA。下丘脑室旁核（PVN）双侧微量注射 GABA 激动剂 muscimol（5mM，500nl）可完全消除 MAP 和肾 SNA 的变化。颈动脉内输注 20 分钟 NaCl 可刺激更大的饮水量增加（1100±75ml），而颈动脉内输注山梨醇（683±125ml）或尿素（0ml）则不能。这些结果表明，急性增加血液钠离子水平会导致清醒绵羊肾 SNA 下降，但对心脏 SNA 无影响。这些影响是由位于血脑屏障外的大脑传感器介导的，这些传感器对钠离子浓度变化的反应比对渗透压的变化更敏感。钠的肾交感神经抑制作用是通过 PVN 中的突触传递途径介导的。
