The role of nitric oxide in lung ischemia and reperfusion
injury.
Moore, Timothy M., Pavel L. Khimenko, Peter S. Wilson, and Aubrey E.
Taylor.
University of South Alabama, College of Medicine, Department of
Physiology, MSB 3024, Mobile, Alabama, 36688
APStracts 3:0166H, 1996.
We studied the effects of nitric oxide synthase (NOS) inhibitors and
nitric oxide (NO.) donors on ischemia and 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 minutes of ischemia followed by 30 minutes
of reperfusion. Lungs that were pretreated with 300 and 600 [mu]M N
-Nitro-L-Arginine-Methyl-Ester (L-NAME); 1, 300, and 600 [mu]M N
-Methyl-L-Arginine (L-NMA); or 600 [mu]M N(5)-(1-Iminoethyl)-L
-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-Nitro-D
-Arginine-Methyl-Ester (D-NAME) 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 sodium bicarbonate 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 [mu]M) and (+) S
-Nitroso-N-acetylpenacillamine (SNAP, 300 [mu]M) both prevented the
increase in Kf,c. associated with I/R. We conclude from these studies
that peroxynitrite does not mediate microvascular permeability
increase following lung I/R injury in this model, and exogenous NO.
does not exacerbate injury, rather it prevents microvascular damage.
Received 8 November 1995; accepted in final form 8 April 1996.
APS Manuscript Number H1045-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96