Mayhan W G
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Brain Res. 1995 Jul 17;686(1):99-103. doi: 10.1016/0006-8993(95)00460-8.
The goal of this study was to determine the role of nitric oxide in disruption of the blood-brain barrier during acute hypertension. We examined the microcirculation of the cerebrum in vivo. Permeability of the blood-brain barrier was quantitated by the formation of venular leaky sites and clearance of fluorescent-labeled albumin (FITC-albumin) before and during phenylephrine-induced acute hypertension. We compared disruption of the blood-brain barrier during acute hypertension in untreated rats and in rats treated for 1 h with topical application of NG-monomethyl-L-arginine (L-NMMA; 100 microM) or NG-nitro-L-arginine methyl ester (L-NAME; 100 microM). Under control conditions, no venular leaky sites were visible and clearance of FITC-albumin was minimal in untreated rats and in rats treated with topical application of nitric oxide synthase inhibitors. Phenylephrine (20 micrograms/kg/min for 5 min) infusion increased systemic arterial pressure by a similar magnitude in all groups of rats and produced disruption of the blood-brain barrier in venules. However, the magnitude of disruption of the blood-brain barrier during acute hypertension was significantly less in rats treated with L-NMMA (52% reduction in the clearance of FITC-albumin) and L-NAME (47% reduction in clearance of FITC-albumin). The findings of the present study suggest that synthesis/release of nitric oxide contributes to disruption of the blood-brain barrier during acute hypertension.
本研究的目的是确定一氧化氮在急性高血压期间血脑屏障破坏中的作用。我们在体内检查了大脑的微循环。在去氧肾上腺素诱导的急性高血压之前和期间，通过形成小静脉渗漏部位和荧光标记白蛋白（异硫氰酸荧光素标记白蛋白）的清除来定量血脑屏障的通透性。我们比较了未治疗大鼠和用局部应用NG-单甲基-L-精氨酸（L-NMMA；100微摩尔）或NG-硝基-L-精氨酸甲酯（L-NAME；100微摩尔）治疗1小时的大鼠在急性高血压期间血脑屏障的破坏情况。在对照条件下，未治疗大鼠和局部应用一氧化氮合酶抑制剂治疗的大鼠中，未见小静脉渗漏部位，异硫氰酸荧光素标记白蛋白的清除率最低。去氧肾上腺素（20微克/千克/分钟，持续5分钟）输注使所有组大鼠的全身动脉压升高幅度相似，并导致小静脉血脑屏障破坏。然而，急性高血压期间血脑屏障的破坏程度在L-NMMA治疗的大鼠（异硫氰酸荧光素标记白蛋白清除率降低52%）和L-NAME治疗的大鼠（异硫氰酸荧光素标记白蛋白清除率降低47%）中明显较小。本研究结果表明，一氧化氮的合成/释放有助于急性高血压期间血脑屏障的破坏。
