Increased expression of nitric oxide synthase in human lung transplants after nitric oxide inhalation

Background. The effects of the ischemia-reperfusion process of organ transplantation on nitric oxide (NO) synthase (NOS) in humans are unknown. The effects of NO inhalation on endogenous NOS expression and activity are controversial. The authors hypothesized that NO inhalation may affect ischemia-reperfusion-induced alterations of the endogenous NOS system. Methods. The authors performed lung biopsy on patients in a randomized phase II clinical trial of NO inhalation during lung transplantation. After lung implantation, 20 ppm of NO or placebo gas was administered 10 min after the start of reperfusion. Lung tissues were collected from 20 patients (NO, n=9; placebo, n = 11) after cold and warm ischemia, 1 hr and 2 hr after reperfusion. The protein levels of NOS isoforms were analyzed by Western blotting and the total NOS activity was measured. Results. The protein levels of inducible NOS did not change significantly in either of the groups. In contrast, during the 2-hr reperfusion period, constitutive NOS (neuronal NOS [nNOS] and endothelial NOS) tended to decrease in the placebo group, but gradually increased in the NO group. After 2 hr of reperfusion, the nNOS protein in the NO group was significantly higher than that in the placebo group (P<0.05). However, the total NOS activity remained at low levels in both groups. Conclusions. NO inhalation-induced increase of constitutive NOS proteins indicates the interaction between inhaled NO molecules and lung tissues. However, the activity of these newly synthesized NOS proteins remains suppressed during the ischemia-reperfusion period of lung transplantation.