Alterations of nitric oxide synthase expression and activity during rat lung transplantation.
Decreased nitric oxide (NO) production has been reported during lung transplantation in patients. To study the effects of ischemia and reperfusion on endogenous NO synthase (NOS) expression, both an ex vivo and an in vivo lung injury model for transplantation were used. Donor rat lungs were flushed with cold low-potassium dextran solution and subjected to either cold (4 degrees C for 12 h) or warm (21 degrees C for 4 h) ischemic preservation followed by reperfusion with an ex vivo model. A significant increase in inducible NOS and a decrease in endothelial NOS mRNA was found after reperfusion. These results were confirmed in a rat single-lung transplant model after warm preservation. Interestingly, protein contents of both inducible NOS and endothelial NOS increased in the transplanted lung after 2 h of reperfusion. However, the total activity of NOS in the transplanted lungs remained at very low levels. We conclude that ischemic lung preservation and reperfusion result in altered NOS gene and protein expression with inhibited NOS activity, which may contribute to the injury of lung transplants.
Liu
M
M
Thoracic Surgery Research Laboratory, Toronto General Hospital, Toronto M5G 2C4, Canada. mingyao.liu@utoronto.ca
Tremblay
L
L
Cassivi
S D
SD
Bai
X H
XH
Mourgeon
E
E
Pierre
A F
AF
Slutsky
A S
AS
Post
M
M
Keshavjee
S
S
D000818:Animals; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D006085:Graft Survival / Q000502:physiology*; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011652:Pulmonary Circulation / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat