Role of nitric oxide in lung ischemia and reperfusion injury.
We studied the effects of nitric oxide synthase (NOS) inhibitors and nitric oxide (NO.) donors on ischemia-reperfusion (I/R)-induced microvascular permeability increase in isolated buffer-perfused rat lungs. Microvascular permeability (Kf,c) was significantly increased in lungs subjected to 45 min of ischemia followed by 30 min of reperfusion. Lungs that were pretreated with 300 and 600 microM N omega-nitro-L-arginine methyl ester (L-NAME), 1, 300, and 600 microM NG-monomethyl-L-arginine (L-NMMA), or 600 microM L-N6-(1-iminoethyl) ornithine (L-NIO) still showed significant increases in Kf,c after I/R. Lungs that were pretreated with 5 mM L-NAME or 5 mM N omega-nitro-D-arginine methyl ester showed no increase in Kf,c after I/R. However, both compounds at these concentrations produced significant decreases in perfusate pH. The decreased pH was responsible for the protective effects, since lungs pretreated with 5 mM L-NAME and supplemented with NaHCO3 to prevent the perfusate pH decrease still showed a significant elevation in Kf,c after I/R. In additional experiments, NO.donors were administered to isolated lungs at the onset of reperfusion. Spermine-NO (100 microM) and S-nitroso-N-acetylpenacillamine (300 microM) both prevented the increase in Kf,c associated with I/R. We conclude from these studies that peroxynitrite does not mediate microvascular permeability increase after lung I/R injury in this model, and exogenous NO. does not exacerbate injury; rather, it prevents microvascular damage.
Moore
T M
TM
Department of Physiology, University of South Alabama College of Medicine, Mobile 36688, USA.
Khimenko
P L
PL
Wilson
P S
PS
Taylor
A E
AE
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester