THE ROLE OF ENDOGENOUS NITRIC-OXIDE IN MODULATING ISCHEMIA-REPERFUSION INJURY IN THE ISOLATED, BLOOD-PERFUSED RAT LUNG

Ischemia-reperfusion (IR) lung injury occurs after various clinical pr ocedures, including cardiopulmonary bypass. It is not clear whether en dogenous nitric oxide (NO) is protective or injurious in lungs subject ed to IR. Thus, in this study we examined the contribution of endogeno us NO to IR injury in isolated, blood-perfused rat lungs. Lungs of mal e Wistar rats (300 g) were subjected to 30 min ischemia and 180 min re perfusion (I30R180). Lungs were sampled for inducible nitric oxide syn thase (i-NOS) mRNA expression (each n = 3) and NOS enzyme activity (ea ch n = 4) at different time points. NOS inhibitors N-G-nitro-L-arginin e-methyl ester (10(-4) M) and aminoguanidine (10(-4) M) were used to s tudy the contribution of NO to IR injury in lungs subjected to I30R30 and I30R180. The contribution of i-NOS to IR lung injury was studied b y inducing i-NOS enzyme with Solmonella lipopolysaccharide, followed b y I30R30. We found that ischemia-reperfusion alone can upregulate i-NO S mRNA and i-NOS enzyme activity (p < 0.05, ANOVA), but downregulate c onstitutive NOS enzyme activity over 180 min reperfusion. Endogenously produced NO is protective against lung injury in I30R180 in normal ra ts and lung injury in I30R30 in septic rats. NO is also pivotal in mai ntaining pulmonary vascular homeostasis in septic rat lungs undergoing IR.