Alteration of nitric oxide and nitric oxide synthase in lung and aorta in hypoxic pulmonary hypertensive rats

AIM To observe the nitric oxide (NO) content and nitric oxide synthase (NOS) activity in lungs, aorta and blood from plasma of pulmonary artery (PA) and thoracic aorta (TA) in hypoxic pulmonary hypertension(HPH) rats. METHODS Twenty-four male SD rats were randomly divided into four groups with 6 rats in each group: normoxic 2 weeks group, normoxic 3 weeks group, hypoxic 2 weeks group and hypoxia 3 weeks group. The animal model of hypoxia pulmonary hypertension was established by intermittent hypoxia (imitation of highland 5000 m). The maximum pulmonary artery pressure (PAP max) and system artery pressure (Psa) were measured by right cardiac catheterization and by cannulating the left common carotid artery (LCCA), respectively. The right ventricle (RV) and left ventricle plus septum (LV+S) of rats were weighed. The method of nitrate reductase was used to determine the changes of NO and NOS activity in the plasma and tissue and immunohistochemistry was used to observe eNOS expression in pulmonary and aorta. RESULTS In the hypoxic groups, PAPmax[(43.4±4.4)mmHg, (51.8±4.2)mmHg]and the RV/(LV+S) (32.3±1.0, 37.0±1.6)increased significantly compared with those in the control groups[(20.8±2.4)mmHg, (21.8±3.9)mmHg, 21.3±1.0, 20.3±1.2, P0.01]. The longer the time exposed to hypoxia, the higher these parameters (P0.01), but there was no difference in Psa between hypoxic groups and normoxic groups. NO content and NOS activity in lung homogenate, plasma of PA and TA in HPH rats decreased significantly compared with those in the correspondingly control group (P0.01) and no difference was found in the NO content of PA and TA. No difference of the NOS activity was found in aorta homogenate among the four groups. The positive expression of eNOS in pulmonary decreased in hypoxic groups compared with that in the normoxic groups but no difference was found in aorta. CONCLUSION NO content and NOS activity in lungs in HPH rats decrease significantly compared with those in control groups, and there is no difference in aorta. The alteration in lungs and aorta in HPH rats may offer some clues to why hypoxia often results in HPH and not hypertension.