NITRIC-OXIDE SYNTHESIS AND REGIONAL CEREBRAL BLOOD-FLOW RESPONSES TO HYPERCAPNIA AND HYPOXIA IN THE RAT
NITRIC-OXIDE SYNTHESIS AND REGIONAL CEREBRAL BLOOD-FLOW RESPONSES TO HYPERCAPNIA AND HYPOXIA IN THE RAT
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DOI：
10.1038/jcbfm.1993.10
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发表时间：
1993-01-01
影响因子：
6.3
通讯作者：
ALBRECHT, RF
中科院分区：
文献类型：
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作者：
PELLIGRINO, DA;KOENIG, HM;ALBRECHT, RF
本实验观察了一氧化氮（NO）合成在高碳酸血症和低氧引起的脑充血反应中的作用。使用放射性标记的微球测量皮质（CX）、皮质下（SC）、脑干（BS）和小脑（CE）的局部CBF（rCBF）。在存在和不存在通过静脉输注硝基-L-精氨酸甲酯（L-NAME，3 mg kg-1 min-1）诱导的NO合酶抑制的情况下，比较大鼠组中对高碳酸血症（PaCO 2 = 70-80 mm Hg）或缺氧（PaO 2 = 40-45 mm Hg）的rCBF反应。在碳酸正常/含氧量正常的条件下给予L-NAME使基线rCBF值降低40-60%，表明脑血管系统中存在NO“张力”。L-NAME的输注导致在所有测量区域中通常伴随高碳酸血症的rCBF增加的显著衰减。在比较生理盐水输注与L-NAME输注大鼠时，rCBF（相对于正常碳酸盐基线值）的增加百分比分别为351%与166%（CX），446%与199%（SC），443%与206%（BS）和483%与1.74%（CE）。相对于基线的rCBF变化（DELTArCBF，ml 100 g-1 min-1）分别为488 vs 57（CX）、570 vs 60（SC）、434 vs 72（BS）和393 vs 45（CE）。这些差异均具有统计学显著性（p < 0.05）。在缺氧期间，与未给予L-NAME的大鼠相比，抑制NO合酶活性导致大部分区域的rCBF（从常氧基线值）显著更大（p < 0.05）的百分比增加。非L-NAME输注大鼠与L-NAME输注大鼠的变化分别为156%与262%（CX）、181%与309%（SC）和210%与462%（BS）。当比较DELTArCBF值（从含氧量正常的基线水平）时，L-NAME组的变化更大，但差异无统计学意义。本研究结果表明，NO的合成是关键参与脑充血反应高碳酸血症，但不是缺氧。事实上，在缺氧组中获得的数据表明，O2供应的减少可能会抑制大脑中NO的产生能力。
The role of nitric oxide (NO) synthesis in the cerebral hyperemic responses to hypercapnia and hypoxia was investigated in anesthetized rats. Regional CBF (rCBF) measurements were obtained in the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) using radiolabeled microspheres. The rCBF responses to either hypercapnia (PaCO2 = 70-80 mm Hg) or hypoxia (PaO2 = 40-45 mm Hg) were compared in rat groups studied in the presence and absence of NO synthase inhibition induced via the intravenous infusion of nitro-L-arginine methyl ester (L-NAME, 3 mg kg-1 min-1). Administration Of L-NAME under normocapnic/normoxic conditions produced a 40-60% reduction in baseline rCBF values, indicating the presence of a NO ''tone'' in the cerebral vasculature. Infusion Of L-NAME resulted in a substantial attenuation, in all regions measured, of the rCBF increases that normally accompany hypercapnia. In comparing saline-infused to L-NAME-infused rats, the percentage increases in rCBF (from normocapnic baseline values) were 351% versus 166% (CX), 446% versus 199% (SC), 443% versus 206% (BS), and 483% versus 1.74% (CE), respectively. The rCBF changes from baseline (DELTArCBF in ml 100 g-1 min-1) were 488 versus 57 (CX), 570 versus 60 (SC), 434 versus 72 (BS), and 393 versus 45 (CE), respectively. These differences were all statistically significant (p < 0.05). During hypoxia, when compared to rats not given L-NAME, inhibition of NO synthase activity resulted in significantly greater (p < 0.05) percentage increases in rCBF (from normoxic baseline values) in most regions. The changes in non-L-NAME- vs. L-NAME-infused rats were 156% versus 262% (CX), 181% versus 309% (SC), and 210% versus 462% (BS), respectively. When the DELTArCBF values (from normoxic baseline levels) were compared, the changes were greater in the L-NAME group, but the differences were statistically insignificant. The results of this study indicated that NO synthesis is critically involved in the cerebral hyperemic response to hypercapnia but not hypoxia. In fact, the data obtained in the hypoxic groups suggested that reductions in O2 supply may inhibit the NO-generating capacity in the brain.