Chi O Z, Chang Q, Wang G, Weiss H R
Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08901-1977, USA.
Anesth Analg. 1997 Feb;84(2):370-5. doi: 10.1097/00000539-199702000-00024.
We performed this study to evaluate the effects of changing the level of nitric oxide (NO) on disruption of the blood-brain barrier (BBB) by hyperosmolar mannitol. Under isoflurane anesthesia, control rats (control group, n = 6) were given infusions with 25% mannitol into the internal carotid artery before measuring the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB). In the CAS group (n = 6), [3-(cis-2,6-dimethyl piperidino)-sydnonimine] (CAS 754), a NO donor, was injected to decrease the mean arterial pressure (MAP) to 55 mm Hg and in the L-NAME group (n = 6), NG-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, was injected before administering mannitol. In additional control animals (control + P group, n = 6) and additional CAS 754-treated animals (CAS + P group, n = 6), phenylephrine was infused to keep MAP at 130 mm Hg during the experimental period. In the control group, with mannitol injection, the Ki of the ipsilateral cortex (IC) where mannitol was injected increased to 4.3 times that of the contralateral cortex (CC) (17.2 +/- 2.9 vs 4.0 +/- 2.6 microliters.g-1.min.1). Without blood pressure control, the Ki of the IC of the CAS group (7.0 +/- 4.5) was lower and that of the L-NAME group (26.2 +/- 12.7) was higher than that of the control animals. At the same MAP, the Ki of the IC of the CAS + P group (9.6 +/- 3.1) was significantly lower than that of the control + P group (21.3 +/- 14.5) or that of the L-NAME group. There was no significant difference in the Ki of the IC between the control + P and the L-NAME groups. In conclusion, L-NAME worsened BBB disruption induced by hyperosmolar solution, which may be due to the pressure effect of L-NAME. CAS 754 was effective in attenuating disruption of the BBB caused by hyperosmolar mannitol. This effect is apparently not due to decreased MAP.
我们进行这项研究以评估改变一氧化氮（NO）水平对高渗甘露醇破坏血脑屏障（BBB）的影响。在异氟烷麻醉下，在测量14C-α-氨基异丁酸（14C-AIB）的转运系数（Ki）之前，向对照大鼠（对照组，n = 6）的颈内动脉输注25%甘露醇。在CAS组（n = 6）中，注射NO供体[3 -（顺式-2,6-二甲基哌啶基）-西多胺]（CAS 754）以将平均动脉压（MAP）降至55 mmHg，在L-NAME组（n = 6）中，在给予甘露醇之前注射NO合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）。在另外的对照动物（对照 + P组，n = 6）和另外的经CAS 754处理的动物（CAS + P组，n = 6）中，在实验期间输注去氧肾上腺素以将MAP维持在130 mmHg。在对照组中，注射甘露醇后，注射甘露醇侧的同侧皮质（IC）的Ki增加至对侧皮质（CC）的4.3倍（17.2±2.9对4.0±2.6微升·克-1·分钟-1）。在未控制血压的情况下，CAS组IC的Ki（7.0±4.5）较低，L-NAME组IC的Ki（26.2±12.7）高于对照动物。在相同的MAP下，CAS + P组IC的Ki（9.6±3.1）显著低于对照 + P组（21.3±14.5）或L-NAME组。对照 + P组和L-NAME组IC的Ki之间无显著差异。总之，L-NAME使高渗溶液诱导的BBB破坏恶化，这可能归因于L-NAME的压力效应。CAS 754可有效减轻高渗甘露醇引起的BBB破坏。这种作用显然不是由于MAP降低所致。
