Differential effects of atrial natriuretic peptide on the brain water and sodium after experimental cortical contusion in the rat
Differential effects of atrial natriuretic peptide on the brain water and sodium after experimental cortical contusion in the rat
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DOI：
10.1097/01.wcb.0000088762.02615.30
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发表时间：
2003-10-01
影响因子：
6.3
通讯作者：
Marmarou, A
中科院分区：
文献类型：
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作者：
Fukui, S;Fazzina, G;Marmarou, A
心房钠尿肽（ANP）通过环鸟苷酸（cGMP）途径对体内水钠的调节起重要作用。虽然ANP已被证明在脑缺血或脑出血中具有保护作用，但其在创伤性脑损伤（TBI）中的作用尚未阐明。我们在此评估了ANP对TBI中脑水和钠的影响。控制皮质撞击（3 mm深度，6 m/sec）用于诱导大鼠实验性皮质挫伤。在损伤后15分钟，使用植入腹膜腔的微型渗透泵开始连续施用ANP 0.2（n = 6）或0.7 μ g/kg/24 h（n = 6）、cGMP类似物（8-溴-cGMP）0.1（n = 5）或0.3 mg/kg/24 h（n = 5）或赋形剂（n = 6）。伤后24小时，ANP以剂量依赖性方式显著加重损伤半球的脑水肿，同时降低两侧半球的脑钠浓度。这些ANP效应可以通过cGMP类似物来模拟。在第二个系列中（n = 20），BBB的完整性进行了评估，通过评价外渗的伊文思蓝染料。ANP或cGMP类似物在损伤后24小时显著加重损伤半球的BBB破坏。这些发现表明，ANP管理加剧脑水肿后，大鼠的实验性皮质挫伤，可能是因为通过cGMP途径的血脑屏障通透性增加，而它降低脑钠水平。
Atrial natriuretic peptide (ANP) plays an important role in the regulation of water and sodium in the body via cyclic GMP (cGMP) pathway. Although ANP has been shown to be protective in cerebral ischemia or intracerebral hemorrhage, its role in traumatic brain injury (TBI) has yet to be elucidated. We herein assessed ANP effects on brain water and sodium in TBI. Controlled cortical impact (3 nun depth, 6 m/sec) was used to induce an experimental cortical contusion in rats. Continuous administration of ANP 0.2 (n = 6) or 0.7 mug/kg/24 h (n = 6), cGMP analogue (8-Bromo-cGMP) 0.1 (n = 5) or 0.3 mg/kg/24 h (n = 5), or vehicle (n = 6) was begun 15 minutes after injury, using a mini-osmotic pump implanted into the peritoneal cavity. At 24 hours after injury, ANP significantly exacerbated brain edema in the injured hemisphere in a dose-dependent manner while it reduced brain sodium concentrations in both hemispheres. These ANP effects could be mimicked by a cGMP analogue. In the second series (n = 20), BBB integrity was assessed by evaluating the extravasation of Evans blue dye. ANP or cGMP analogue significantly worsened BBB disruption in the injured hemisphere at 24 hours after injury. These findings suggest that ANP administration exacerbates brain edema after the experimental cortical contusion in rats, possibly because of an increase in the BBB permeability via cGMP pathway, whereas it reduces brain sodium levels.