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.
Cardella
Jonathan A
JA
Thoracic Surgery Research Laboratory, University Health Network, Toronto General Hospital, and Department of Surgery and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Keshavjee
Shaf H
SH
Bai
Xiao-Hui
XH
Yeoh
Jin-Soon
JS
Granton
John T
JT
Meade
Maureen O
MO
Matte-Martyn
Andrea
A
Waddell
Thomas K
TK
Liu
Mingyao
M
D000280:Administration, Inhalation; D000328:Adult; D001706:Biopsy; D002423:Cause of Death; D005260:Female; D006801:Humans; D008168:Lung / Q000201:enzymology; D016040:Lung Transplantation / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D010919:Placebos; D015424:Reperfusion
D010919:Placebos; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase