Oxidant-increased endothelial permeability: prevention with phosphodiesterase inhibition vs. cAMP production.
Oxidant-increased endothelial permeability: prevention with phosphodiesterase inhibition vs. cAMP production.
复制标题
氧化剂增加的内皮通透性：通过磷酸二酯酶抑制与 cAMP 产生进行预防。
DOI：
10.1152/jappl.2000.88.3.835
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Minnear,FL
中科院分区：
文献类型：
--
作者：
Waypa,GB;Morton,CA;Vincent,PA;MahoneyJr,JR;Johnston3rd,WK;Minnear,FL
本研究的目的是确定过氧化氢（H2 O2）是否会增加离体大鼠肺的经血管白蛋白清除率和肺重量，以及cAMP增强剂后处理是否可以防止这些增加。通过125 I标记的白蛋白清除率（125 I-白蛋白流量/125 I-白蛋白灌注液浓度）评估给定液体过滤时的经血管白蛋白清除率。经血管白蛋白清除率与液体滤过率的非线性回归分析得出了渗透性-表面积乘积（PS）和反射系数（λ）的值。H_2O_2使肺重量从对照值0.93降低到0.38，不改变PS，并增加肺重量。用β2-肾上腺素能受体激动剂异丙肾上腺素后处理，使H2 O2诱导的肺重量下降减少至0.65，并增加肺重量。用磷酸二酯酶4抑制剂CP-80633后处理，进一步降低了H2 O2诱导的肺重量下降至0.79，并阻止了肺重量的增加。在异丙肾上腺素或CP-80633存在下，H_2O_2使PS增加。因此，H2 O2增加了白蛋白在完整肺血管中的对流和扩散清除率。此外，抑制cAMP代谢更有效地衰减H2 O2诱导的对流白蛋白清除率和肺重量的增加相比，刺激cAMP的生产。
The present objective was to determine whether hydrogen peroxide (H2O2) increases transvascular albumin clearance and lung weight in an isolated rat lung and whether posttreatment with cAMP-enhancing agents can prevent these increases. Transvascular albumin clearance was assessed by125I-labeled albumin clearance (125I-albumin flux/perfusate concentration of125I-albumin) at a given fluid filtration. Nonlinear regression analysis of transvascular albumin clearance vs. fluid filtration yielded values for the permeability-surface area product (PS) and the reflection coefficient (ς). H2O2decreased ς from a control value of 0.93 to 0.38, did not changePS, and increased lung weight. Posttreatment with isoproterenol, a β2-adrenergic-receptor agonist, reduced the H2O2-induced decrease in ς to 0.65 and augmented the increase in lung weight. Posttreatment with CP-80633, a phosphodiesterase 4 inhibitor, further reduced the H2O2-induced decrease in ς to 0.79 and blocked the rise in lung weight. In the presence of isoproterenol or CP-80633, H2O2increasedPS. Therefore, H2O2increased the convective and diffusive clearances of albumin across an intact pulmonary vasculature. Furthermore, inhibition of cAMP metabolism more effectively attenuated the H2O2-induced increases in convective albumin clearance and lung weight as compared with stimulation of cAMP production.