EFFECTS OF NW-NITRO‐L-ARGININE AND DEXAMETHASONE ON EARLY EVENTS FOLLOWING LIPOPOLYSACCHARIDE INJECTION: OBSERVATIONS IN THE HAMSTER CHEEK POUCH MICROCIRCULATION
EFFECTS OF NW-NITRO‐L-ARGININE AND DEXAMETHASONE ON EARLY EVENTS FOLLOWING LIPOPOLYSACCHARIDE INJECTION: OBSERVATIONS IN THE HAMSTER CHEEK POUCH MICROCIRCULATION
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NW-硝基-L-精氨酸和地塞米松对脂多糖注射后早期事件的影响：仓鼠颊囊微循环的观察
DOI：
10.1097/00024382-199405000-00005
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发表时间：
1994
期刊：
影响因子：
3.1
通讯作者：
G. Rubanyi
中科院分区：
文献类型：
--
作者：
E. Bouskela;G. Rubanyi
用大肠杆菌脂多糖（LPS）处理雄性仓鼠，观察了左旋硝基精氨酸（L-NAG）和地塞米松对内毒素血症早期微循环变化的影响。通过活体显微镜和平均动脉和静脉压，平均小动脉内径，自发性小动脉血管运动，微血管血流量，大分子渗透性，白细胞粘附，和平均生存时间进行了研究，在动物单独或LPS与L-NAG，组成型和诱导型NO合成酶（NO）的抑制剂的组合治疗。静脉注射LPS（100 mg/kg）引起平均动脉血压（MABP）和小动脉血流量显着降低。观察到的小动脉扩张，自发性血管运动停止。联合LPS + L-NAG，静脉内给药，防止降低MABP和血管舒张，但没有帮助减少小动脉血流量或停止血管舒缩。为了分离两种NO的作用，用地塞米松（10 mg/kg，也静脉内）预处理一组仓鼠，地塞米松抑制诱导型NO合酶（iNO）的诱导。在这一组中，低血压，血管舒张和血管舒缩停止得到预防，但小动脉血流量的减少不受影响。LPS + L-NAG联合用药组的平均生存时间（35 ± 6 h）显著低于单纯LPS组（56 ± 7 h），地塞米松预处理组的平均生存时间（92 ± 5 h）显著高于单纯LPS组（56 ± 7 h）。局部加入L-NAG（1.3 ng/ml/min）并不显著改变局部单独应用LPS（0.7 μg/ml/min）所观察到的大分子渗透性和白细胞粘附增加。我们的研究结果表明，增加的NO生产的iNOs后LPS治疗可能会导致显着的微循环障碍的仓鼠颊囊。他们还表明，使用非选择性NO合酶抑制剂可能是有害的内毒素休克，可能是因为它抑制iNO似乎有益和组成型NO合酶（cNO）似乎有害。
The effects of NW-nitro-L-arginine (L-NAG) and dexamethasone in the microcirculatory changes observed in early stages of endotoxemia was investigated in male hamsters treated with Escherichia coli lipopolysaccharide (LPS). The cheek pouch was studied in vivo by means of intravital microscopy and mean arterial and venous pressures, mean arteriolar internal diameter, spontaneous arteriolar vasomotion, microvascular blood flow, macromolecular permeability, leukocyte adhesion, and mean survival time were evaluated in animals treated with either LPS alone or the combination of LPS with L-NAG, an inhibitor of both the constitutive and inducible NO synthases (NOs). The intravenous injection of LPS (100 mg/kg) elicited a significant reduction in mean arterial blood pressure (MABP) and arteriolar blood flow. The observed arterioles dilated and the spontaneous vasomotion ceased. The combination LPS + L-NAG, both given intravenously, prevented the reduction of MABP and the vasodilation but did not help either the reduction of arteriolar blood flow or the cessation of vasomotion. In order to separate the effect of the two NOs, a group of hamsters was pretreated with dexamethasone (10 mg/kg, also intravenously) which inhibits the induction of the inducible NO synthase (iNOs). In this group, the hypotension, vasodilation, and cessation of vasomotion were prevented but the decrease in arteriolar blood flow was not affected. The mean survival time was significantly decreased by the combination of LPS + L-NAG (35 ± 6 h) and significantly increased by the pretreatment with dexamethasone (92 ± 5 h) compared to LPS alone (56 ± 7 h). Topical addition of L-NAG (1.3 ng/ml/min) did not significantly change the increased macromolecular permeability and leukocyte adhesion observed with the topical application of LPS (0.7 μg/ml/min) alone. Our results suggest that the increased NO production by the iNOs after LPS treatment could cause significant dysfunction in the microcirculation of the hamster cheek pouch. They also indicate that the use of nonselective NO synthase inhibitors could be detrimental in endotoxic shock, probably because it inhibits the iNOs which seems beneficial and the constitutive NO synthase (cNOs) which seems deleterious.