COMPOUNDS THAT INCREASE CAMP PREVENT ISCHEMIA-REPERFUSION PULMONARY CAPILLARY INJURY
COMPOUNDS THAT INCREASE CAMP PREVENT ISCHEMIA-REPERFUSION PULMONARY CAPILLARY INJURY
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DOI：
10.1152/jappl.1992.72.2.492
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发表时间：
1992-02-01
影响因子：
3.3
通讯作者：
TAYLOR, AE
中科院分区：
文献类型：
--
作者：
ADKINS, WK;BARNARD, JW;TAYLOR, AE
本研究评估了增加腺苷 3',5'-环单磷酸 (cAMP) 的化合物对离体血液灌注兔肺缺血再灌注 (I-R) 引起的肺毛细血管通透性和血管阻力变化的生理影响。 cAMP 通过 1) 异丙肾上腺素 (ISO, 10(-5) M) β-肾上腺素刺激，2) 福司可林 (FSK, 10(-5) M) 腺苷酸环化酶后 β-受体刺激，3) 和二丁酰 cAMP (DBcAMP, 1 mM)（一种 cAMP 类似物）升高。 通过测定毛细血管滤过系数（K(f,c)）来评估血管通透性，并使用双闭塞技术测量毛细血管压力。 根据测量的肺动脉、静脉和毛细血管压力和血流量计算总血管阻力、动脉血管阻力和静脉血管阻力。 缺血 2 小时后再灌注显着 (P < 0.05) 增加 K(f,c)（从 0.115 +/- 0.028 到 0.224 +/- 0.040 ml.min-1.cmH2O-1.100 g-1）。 当再灌注时向灌注液中添加 ISO、FSK 或 DBcAMP 时，可以防止这些 I-R 引起的毛细血管通透性变化（0.110 +/- 0.022 和 0.103 +/- 0.021、0.123 +/- 0.029 和 0.164 +/- 0.024、以及 0.153 +/- 0.030 和 0.170分别为 +/- 0.027 ml.min-1.cmH2O-1.100 g-1）。 I-R 显着增加总血管阻力、动脉血管阻力和静脉血管阻力。 ISO、FSK 和 DBcAMP 也可以阻止血管阻力的增加。 这些数据表明，β-肾上腺素能刺激、腺苷酸环化酶的后β-受体激活和DBcAMP通过涉及细胞内cAMP水平增加的机制，防止离体兔肺中I-R引起的肺血管通透性和血管阻力的变化。 cAMP水平升高导致内皮细胞松弛，导致其细胞间连接尺寸减小，或者抑制中性粒细胞破坏毛细血管内皮屏障的能力。
This study evaluated the physiological effects of compounds that increase adenosine 3',5'-cyclic monophosphate (cAMP) on changes in pulmonary capillary permeability and vascular resistance induced by ischemia-reperfusion (I-R) in isolated blood-perfused rabbit lungs. cAMP was elevated by 1) beta-adrenergic stimulation with isoproterenol (ISO, 10(-5) M), 2) post-beta-receptor stimulation of adenylate cyclase with forskolin (FSK, 10(-5) M), 3) and dibutyryl cAMP (DBcAMP, 1 mM), a cAMP analogue. Vascular permeability was assessed by determining the capillary filtration coefficient (K(f,c)), and capillary pressure was measured using the double occlusion technique. The total, arterial, and venous vascular resistances were calculated from measured pulmonary arterial, venous, and capillary pressures and blood flow. Reperfusion after 2 h of ischemia significantly (P < 0.05) increased K(f,c) (from 0.115 +/- 0.028 to 0.224 +/- 0.040 ml.min-1.cmH2O-1.100 g-1). These I-R-induced changes in capillary permeability were prevented when ISO, FSK, or DBcAMP was added to the perfusate at reperfusion (0.110 +/- 0.022 and 0.103 +/- 0.021, 0.123 +/- 0.029 and 0.164 +/- 0.024, and 0.153 +/- 0.030 and 0.170 +/- 0.027 ml.min-1.cmH2O-1.100 g-1, respectively). I-R significantly increased total, arterial, and venous vascular resistances. These increases in vascular resistance were also blocked by ISO, FSK, and DBcAMP. These data suggest that beta-adrenergic stimulation, post-beta-receptor activation of adenylate cyclase, and DBcAMP prevent the changes in pulmonary vascular permeability and vascular resistances caused by I-R in isolated rabbit lungs through a mechanism involving an increase in intracellular levels of cAMP. The increased cAMP level causes either a relaxation of endothelial cells, resulting in a decreased size of their intercellular junctions, or inhibits the ability of neutrophils to damage the capillary endothelial barrier.