AUGMENTATION OF HYPOXIC PULMONARY VASOCONSTRICTION IN THE ISOLATED PERFUSED RAT LUNG BY INVITRO ANTAGONISTS OF ENDOTHELIUM-DEPENDENT RELAXATION
AUGMENTATION OF HYPOXIC PULMONARY VASOCONSTRICTION IN THE ISOLATED PERFUSED RAT LUNG BY INVITRO ANTAGONISTS OF ENDOTHELIUM-DEPENDENT RELAXATION
复制标题
DOI：
10.1172/jci113757
复制
发表时间：
1988-11-01
影响因子：
15.9
通讯作者：
ROSE, CE
中科院分区：
文献类型：
--
作者：
BRASHERS, VL;PEACH, MJ;ROSE, CE
内皮在完整肺血管床缺氧收缩中的作用尚未明确阐明。为了测试内皮源性舒张因子（EDRF）在缺氧性升压反应中的可能作用，制备了用甲氨蝶呤处理的雄性Sprague-Dawley大鼠的分离的全血灌注大鼠肺。进行了三种方案，包括：（a）生理盐水（对照）;（B）假定的EDRF抑制剂，二十碳四炔酸（ETYA，1 × 10 - 2 mol/L）; 10-4 M）或去甲二氢愈创木酸（NDGA，1x. 10-4 M）与载体DMSO的比较;和（c）推定的EDRF抑制剂氢醌（HQ，1 × 1000）与载体DMSO的比较。10-4 M）与载体乙醇（ETOH）。在施用盐水、抑制剂或媒介物之前和之后测量对血管紧张素II（Ang II，0.25 μ g）注射与6分钟低氧通气（3%O2，5%CO2）交替的肺加压反应。给予EDRF抑制剂ETYA、NDGA和HQ后，缺氧性升压反应明显增强，而对照组则无此现象（P < 0.05）。在单独的实验中，肺用去甲肾上腺素（1 × 10 - 4）预收缩。10-6 M）用依地酚铵（1 × 10 - 4）预处理。10-4 M），然后观察内皮依赖性血管舒张剂对乙酰胆碱的反应，乙酰胆碱的剂量逐渐增加（1 × 10 - 6 μ g/ml）。10-7-1 ×10-4 M）。ETYA、NDGA或HQ的给药消除了所观察到的对乙酰胆碱的血管舒张作用，这在单独的载体中没有观察到（P < 0.01）。 这些研究表明，内皮细胞在肺血管对肺泡缺氧的反应性中起重要作用，可能通过释放一种松弛因子来减弱肺动脉收缩的程度。
The role of the endothelium in hypoxic constriction of the intact pulmonary vascular bed has not been clearly elucidated. To test for a possible role for endothelium-derived relaxing factor(s) (EDRF) in the hypoxic pressor response, isolated, whole blood-perfused rat lungs from male Sprague-Dawley rats treated with meclofenamate were prepared. Three protocols were performed, including: (a) normal saline (control); (b) the putative EDRF inhibitors, eicosatetraynoic acid (ETYA, 1 .times. 10-4 M) or nordihydroguaiaretic acid (NDGA, 1 .times. 10-4 M) versus vehicle DMSO; and (c) the putative EDRF inhibitor hydroquinone (HQ, 1 .times. 10-4 M) versus vehicle ethyl alcohol (ETOH). The pulmonary pressor response to angiotensin II (Ang II, 0.25 .mu.g) injections alternated with 6-min periods of hypoxic ventilation (3% O2, 5% CO2) was measured before and after the administration of saline, inhibitors, or vehicles. The administration of the EDRF inhibitors ETYA, NDGA, and HQ resulted in a marked accentuation of the hypoxic pressor response that was not seen in the controls (P < 0.05). In separate experiments, lungs precontracted with norepinephrine (1 .times. 10-6 M) were pretreated with edrophonium (1 .times. 10-4 M) and then observed for endothelium-dependent vasodilator responses to acetylcholine at increasing doese (1 .times. 10-7-1 .times. 10-4 M). Administration of ETYA, NDGA, or HQ abrogated the observed vasodilatation to acetylcholine, which was not seen with vehicles alone (P < 0.01). These studies suggest an important role for the endothelium in pulmonary vascular responsiveness to alveolar hypoxia through possible release of a relaxing factor(s) that attenuates the degree of pulmonary arterial constriction.