Dysfunction of cGMP-mediated pulmonary vasorelaxation in endotoxin-induced acute lung injury.
Dysfunction of cGMP-mediated pulmonary vasorelaxation in endotoxin-induced acute lung injury.
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内毒素引起的急性肺损伤中 cGMP 介导的肺血管舒张功能障碍。
DOI：
10.1152/ajplung.1995.268.6.l1029
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Harken,AH
中科院分区：
文献类型：
--
作者：
Fullerton,DA;McIntyreJr,RC;Hahn,AR;Agrafojo,J;Koike,K;Meng,X;Banerjee,A;Harken,AH
本实验研究了内毒素诱导的急性肺损伤大鼠肺血管舒张的内皮依赖性和非依赖性环鸟苷酸（cGMP）机制。内毒素处理（20 mg/kg ip）后6小时，在用苯丙氨酸预收缩的离体肺动脉环中，绘制乙酰胆碱（ACh）、A23187和硝普钠（SNP）以及8-溴鸟苷3 '，5'-环一磷酸（8-BrcGMP）（10（-9）至10（-4）M）的浓度-反应曲线。内毒素处理导致肺中性粒细胞蓄积（髓过氧化物酶测定，28 +/- 6单位/g肺组织，对照组为1.8 +/- 1）和肺渗漏（肺/血125 I标记白蛋白比，0.06 +/- 0.01，对照组为0.028 +/- 0.01）显著增加，以及肺血管内皮损伤的组织学证据。浓度-反应曲线表明，肺血管舒张的机制，需要产生cGMP的内皮依赖性（受体依赖性，ACh，和受体非依赖性，A23187）或内皮非依赖性（SNP）途径后，内毒素治疗显着受损。用cGMP类似物8-BrcGMP刺激的舒张与对照没有不同。肺血管平滑肌能够在内毒素处理后响应于cGMP而松弛，但需要产生cGMP的内皮依赖性和非依赖性途径的松弛显著受损。
Endothelial-dependent and -independent cGMP-mediated mechanisms of pulmonary vasorelaxation were studied in endotoxin-induced acute lung injury in the rat. Concentration-response curves were generated (10(-9) to 10(-6) M) for acetylcholine (ACh), A23187, and sodium nitroprusside (SNP) and for 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) (10(-9) to 10(-4) M) in isolated pulmonary arterial rings preconstricted with phenylephrine 6 h after endotoxin treatment (20 mg/kg ip). Endotoxin treatment produced significantly increased lung neutrophil accumulation (myeloperoxidase assay, 28 +/- 6 units/g lung tissue vs. 1.8 +/- 1 in controls) and lung leakage (lung/blood 125I-labeled albumin ratio, 0.06 +/- 0.01 vs. 0.028 +/- 0.01 in controls) as well as histological evidence of pulmonary vascular endothelial damage. The concentration-response curves demonstrated that pulmonary vasorelaxation by mechanisms that require generation of cGMP by either endothelial-dependent (both receptor-dependent, ACh, and receptor-independent, A23187) or endothelial-independent (SNP) pathways were significantly impaired after endotoxin treatment. Relaxation by stimulation with the cGMP analogue 8-BrcGMP was not different from control. Pulmonary vascular smooth muscle is able to relax in response to cGMP after endotoxin treatment, but relaxation by endothelial-dependent and -independent pathways that require generation of cGMP is significantly impaired.