Jiang Leifu, Quarck Rozenn, Janssens Stefan, Pokreisz Peter, Demedts Maurits, Delcroix Marion
Department of Pneumology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
Pflugers Arch. 2006 May;452(2):213-21. doi: 10.1007/s00424-005-0028-3. Epub 2006 Jan 11.
Aerosol gene transfer of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) to rat lungs increased NOS expression and activity, and prevented hypoxic pulmonary vasoconstriction (HPV) in vivo. Hereby, we examined the effect of eNOS and iNOS aerosol gene transfer on the endothelium-dependent relaxation (EDR) and on acute HPV in isolated rat pulmonary arteries. Changes in isometric forces were recorded in organ baths for large conduit arteries (diameter 1.8+/-0.1 mm) and in a wire myograph for small resistance arteries (258+/-35 microm). Male Wistar rats were randomly aerosolized with adenovirus (Ad) encoding beta-galactosidase (control), eNOS, or iNOS. Four days later, exhaled nitric oxide was measured, NOS expression within rat lungs was evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry, vasoconstricting agonist and acetylcholine concentration response curves were generated, and the time course of HPV was recorded. Human eNOS and murine iNOS were expressed within rat lung tissue mostly in parenchyma and endothelial cells. Large arteries isolated from Ad-i, eNOS-aerosolized rats developed lower agonist-induced tension than those of control rats. The first and second contractions of the HPV were smaller in the Ad-i, eNOS-aerosolized rats. Contractions were modestly, but significantly and inversely, related to exhaled NO. Agonist- and hypoxia-induced contractions were even more reduced after eNOS aerosolization. There was no significant effect on EDR and no notable difference between small and large vessels. We conclude that adenovirus (Ad)-mediated NOS gene transfer can counteract both pharmacologically and hypoxia-induced increases in pulmonary vascular tone in isolated rat pulmonary arteries. eNOS seems as efficient as iNOS in regulating pulmonary vascular tone.
将内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）通过气溶胶基因转移至大鼠肺内，可增加一氧化氮合酶的表达和活性，并在体内预防低氧性肺血管收缩（HPV）。在此，我们研究了eNOS和iNOS气溶胶基因转移对离体大鼠肺动脉内皮依赖性舒张（EDR）和急性HPV的影响。在器官浴槽中记录大的传导动脉（直径1.8±0.1毫米）的等长力变化，在钢丝肌动描记器中记录小的阻力动脉（258±35微米）的等长力变化。将雄性Wistar大鼠随机用编码β-半乳糖苷酶（对照）、eNOS或iNOS的腺病毒（Ad）进行气溶胶处理。4天后，测量呼出的一氧化氮，通过定量实时聚合酶链反应和免疫组织化学评估大鼠肺内的一氧化氮合酶表达，生成血管收缩激动剂和乙酰胆碱浓度反应曲线，并记录HPV的时间进程。人eNOS和小鼠iNOS主要在大鼠肺组织的实质和内皮细胞中表达。从Ad-i、eNOS气溶胶处理的大鼠分离出的大动脉，其激动剂诱导的张力低于对照大鼠。Ad-i、eNOS气溶胶处理的大鼠中HPV的第一次和第二次收缩较小。收缩与呼出的一氧化氮呈适度但显著的负相关。eNOS气溶胶处理后，激动剂和低氧诱导的收缩进一步减少。对EDR无显著影响，小血管和大血管之间无明显差异。我们得出结论，腺病毒（Ad）介导的一氧化氮合酶基因转移可在药理学上和低氧诱导的离体大鼠肺动脉血管张力增加方面发挥对抗作用。在调节肺血管张力方面，eNOS似乎与iNOS一样有效。
