Zingarelli B, Squadrito F, Altavilla D, Calapai G, Campo G M, Calò M, Saitta A, Caputi A P
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
J Cardiovasc Pharmacol. 1992 Jun;19(6):982-6. doi: 10.1097/00005344-199206000-00021.
Hypovolemic hemorrhagic shock was induced in rats by intermittently withdrawing blood from an iliac catheter for 20 min until mean arterial blood pressure (MAP) decreased to 30 mm Hg. Survival rate, survival time, plasma myocardial depressant factor (MDF) activity, MAP, and microscopic gastric alterations were then evaluated. NG-nitro-L-arginine methyl-ester (L-NAME), a selective inhibitor of nitric oxide (NO) production from L-arginine, was injected intravenously (i.v.) after the bleeding was discontinued. Untreated hemorrhagic shocked rats died in 27 +/- 3.3 min, had enhanced plasma activity of MDF, and exhibited hemorrhagic infiltrates in gastric fundus mucosa. L-NAME (5 and 10 mg/kg) significantly increased survival rate and time, blunted the increase in plasma MDF activity, and protected against the gastric lesions induced by hemorrhagic hypovolemic shock. All these protective effects were reversed by a bolus of L-arginine (30 mg/kg/i.v.), given 2 min after administration of L-NAME. Our findings suggest that NO production plays an important role in the pathophysiology of hemorrhagic shock.
通过从大鼠髂静脉导管间歇性采血20分钟，直至平均动脉血压（MAP）降至30 mmHg，诱导大鼠发生低血容量性出血性休克。然后评估存活率、存活时间、血浆心肌抑制因子（MDF）活性、MAP以及胃组织的微观改变。出血停止后，静脉注射L-精氨酸一氧化氮（NO）生成的选择性抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）。未经治疗的出血性休克大鼠在27±3.3分钟内死亡，血浆MDF活性增强，胃底黏膜出现出血性浸润。L-NAME（5和10 mg/kg）显著提高了存活率和存活时间，抑制了血浆MDF活性的升高，并预防了出血性低血容量性休克诱导的胃损伤。在给予L-NAME 2分钟后静脉注射一剂L-精氨酸（30 mg/kg）可逆转所有这些保护作用。我们的研究结果表明，NO生成在出血性休克的病理生理学中起重要作用。
