Sadoshima S, Nagao T, Okada Y, Fujii K, Ibayashi S, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Brain Res. 1997 Jan 9;744(2):246-52. doi: 10.1016/S0006-8993(96)01063-3.
The effects of L-arginine (a precursor of nitric oxide, NO) on cerebral blood flow (CBF), cerebrovascular resistance (CVR) and metabolites in the ischemic brain were examined in spontaneously hypertensive rats with bilateral carotid artery occlusion for 30 min followed by 60 min-recirculation. The administration of L-arginine (300 mg/kg, i.v.) increased the CBF by an average of 11 ml x 100 g-1 x min-1 (P < 0.05 vs. at rest), and N(omega)-nitro-L-arginine (L-NNA, an inhibitor of NO synthase, 5 mg/kg, i.v.) reduced the CBF by 5-6 ml x 100 g-1.min-1 with increase in the mean arterial pressure by 26 mmHg. During ischemia the CBF significantly decreased to below 8% of the resting values in all rats. The largest blood flow in postischemic hyperemia was 171 +/- 9% of the resting CBF in the rats with L-arginine (P < 0.05 vs. L-NNA and saline), followed by 126 +/- 5 with saline and 109 +/- 3 with L-NNA. The CVR at 60 min of recirculation was 3.291 +/- 0.144 mmHg . ml-1. 100 g-1 .min-1 in the rats with saline, remained low level of 2.711 +/- 0.124 with L-arginine (P < 0.01 vs. L-NNA and P < 0.05 vs. saline) and in contrast, significantly increased to 5.732 +/- 0.184 with L-NNA (P < 0.01 vs. L-arginine and saline, respectively). Tissue lactate with saline increased 2.3-fold at 60 min of recirculation, whereas the increase was inhibited to 1.4-fold after L-arginine treatment (P < 0.01 vs. L-NNA) and in contrast, significantly increased 5.7-fold with L-NNA. The ATP and glucose levels were better preserved in the rats with L-arginine than in those with L-NNA or saline. These findings support that the enhanced postischemic hyperemia is beneficial to the ischemic brain and the administration of L-arginine may be potentially useful for the treatment of acute stroke.
在双侧颈动脉闭塞30分钟后再灌注60分钟的自发性高血压大鼠中，研究了L-精氨酸（一氧化氮，NO的前体）对脑血流量（CBF）、脑血管阻力（CVR）和缺血性脑代谢物的影响。静脉注射L-精氨酸（300mg/kg）使CBF平均增加11ml×100g-1×min-1（与静息状态相比，P<0.05），而静脉注射N（ω）-硝基-L-精氨酸（L-NNA，一种NO合酶抑制剂，5mg/kg）使CBF降低5-6ml×100g-1.min-1，同时平均动脉压升高26mmHg。在缺血期间，所有大鼠的CBF均显著降至静息值的8%以下。在L-精氨酸处理的大鼠中，缺血后充血时的最大血流量为静息CBF的171±9%（与L-NNA和生理盐水相比，P<0.05），其次，生理盐水处理组为126±5，L-NNA处理组为109±3。再灌注60分钟时，生理盐水处理组大鼠的CVR为3.291±0.144mmHg·ml-1·100g-1·min-1，L-精氨酸处理组保持在较低水平，为2.711±0.124（与L-NNA相比，P<0.01；与生理盐水相比，P<0.05），相反，L-NNA处理组显著升高至5.732±0.184（分别与L-精氨酸和生理盐水相比，P<0.01）。生理盐水处理组在再灌注60分钟时组织乳酸增加2.3倍，而L-精氨酸处理后增加被抑制至1.4倍（与L-NNA相比，P<0.01），相反，L-NNA处理组显著增加5.7倍。与L-NNA或生理盐水处理组相比，L-精氨酸处理组大鼠的ATP和葡萄糖水平保存得更好。这些发现支持缺血后充血增强对缺血性脑有益，并且L-精氨酸给药可能对急性中风的治疗具有潜在作用。
