[Preventive effect of endothelial nitric oxide synthase gene transfer on chronic hypoxic pulmonary hypertension in rats].

OBJECTIVE: To investigate the preventive effect of endothelial nitric oxide synthase (eNOS) gene transfer on chronic hypoxic pulmonary hypertension (CHPH) in rats. METHODS: Twenty-four male Wistar rats were randomly divided into four groups with 6 rats in each group: normoxia group (group N), hypoxia group (group H), hypoxia with LacZ group (group H-LacZ) and hypoxia with eNOS group (group H-eNOS). AdCMVceNOS, AdCMVLacZ or normal saline (NS) was injected intratracheally 3 days before the beginning of exposure to normoxia or hypoxia. Rats in group H-eNOS received 50 microl of AdCMVceNOS (5 x 10(12)pfu/L), rats in group H-LacZ received equal dose of AdCMVLacZ, rats in group N and group H received equal dose of NS. Hemodynamic parameters [including mean systemic arterial pressure (MSAP), heart rate (HR) and mean pulmonary arterial pressure (MPAP)], pulmonary vascular remodeling (percentage of muscularized arteries in small pulmonary vessels) and right ventricular hypertrophy (ratio of right ventricle to left ventricle + septum weight) were measured after 2 weeks of exposure to normoxia or hypoxia. The expression of eNOS, cyclic guanosine monophosphate (cGMP) and nitric oxide (NO) level were also measured in lungs. RESULTS: The MPAP, right ventricular hypertrophy index and pulmonary vascular remodeling in rats in group H-eNOS were obviously lower than those in group H and H-LacZ, but higher than that in group N (all P<0.01). There was no significant difference with regard to HR and MSAP in rats in all groups (all P>0.05). The eNOS protein in group H and H-LacZ was obviously higher than that in group N, but obviously lower than that in group H-eNOS (all P<0.01). The NO level in rat lungs in group H and H-LacZ was obviously lower than that in group N, and value in group H-eNOS was higher than that in the other groups (P<0.05 or P<0.01). With regard to cGMP in rat lungs, there was no significant difference among group N, H and H-LacZ (all P>0.05), but they were all obviously lower than that in group H-eNOS (all P<0.01). CONCLUSION: Intratracheal eNOS gene transfer upregulates the activity of eNOS protein, elevates the level of NO/cGMP in lungs, and alleviates CHPH in rats.