Therapy of experimental pulmonary hypertension by cyclic GMP related gene transfer

在所有情况下，引起肺动脉高压的血管改变包括正常非肌化的外周肺动脉的新肌化，肌肉动脉的中层肥厚，以及血管结缔组织蛋白如胶原和弹性蛋白的增加。持续吸入NO及NO前体L-精氨酸可预防慢性低氧大鼠高血压性肺血管病变的发生。NO可增加cGMP的表达。心钠素(ANP)也可增加cGMP。我们确定肺内ANP基因转移是否能预防慢性缺氧性肺动脉高压肺血管改变的发生。用新型非病毒型日本血凝病毒(HEJ)囊膜载体气管内注射导入ANP基因。ANP基因转移可防止血管病变和肺动脉高压的发生。

In all condition causing pulmonary hypertension vascular changes includes new muscularization of normally nonmuscularized peripheral pulmonary arteries, medial hypertrophy of muscular artery and increase in vascular connective tissue protein such as collagen and elastin. Continuous NO inhalation and NO precursor L-arginine prevented the development of hypertensive pulmonary vascular changes in chronic hypoxia. NO increases cyclic-GMP. Atrial natriuretic peptide (ANP) also increase cyclic-GMP. we determined if ANP gene transfer in lung prevent the development of pulmonary vascular changes in chronic hypoxia-induced pulmonary hypertension. ANP gene was transferred by novel-nonviral HVJ (hemagglutinating virus of Japan) envelope vector by intratracheal injection. ANP gene transfer prevented the development of the vascular changes and pulmonary hypertension.