Therapy of experimental pulmonary hypertension by cyclic GMP related gene transfer

在所有引起肺动脉高压的疾病中，血管变化包括正常非肌化外周肺动脉的新肌化、肌性动脉中膜肥大和血管结缔组织蛋白（如胶原蛋白和弹性蛋白）增加。持续吸入NO和NO前体L-精氨酸可预防慢性缺氧时高血压肺血管变化的发生。NO增加环GMP。心房利钠肽（ANP）也增加环GMP。我们确定肺内ANP基因转移是否阻止慢性缺氧诱导的肺动脉高压中肺血管变化的发展。利用新型非病毒HVJ（日本血凝病毒）包膜载体，经腹腔注射法将ANP基因导入小鼠体内。ANP基因转染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.