Inducible nitric oxide production is an adaptation to cardiopulmonary bypass-induced inflammatory response

Background. Cardiopulmonary bypass (CPB) increases nitric oxide (NO) production by the activation of NO synthases (NOS). However, the role of NO from inducible NOS (iNOS) in CPB-induced inflammatory response remains unclear. We examined the effect of a selective iNOS inhibitor, aminoguanidine, on CPB-induced inflammatory response in a rat-CPB model. Methods. Adult Sprague-Dawley rats underwent 60 minutes of CPB (100 mL · kg−1 · min−1, 34°C). Group A (n = 10) received 100 mg/kg of aminoguanidine intraperitoneally 30 minutes before the initiation of CPB, and group B (n = 10) served as controls. Results. There were significant time-dependent changes in plasma interleukin (IL)-6, IL-8, nitrate + nitrite, the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr, an indicator of peroxynitrite formation), and respiratory index (RI). Three hours after CPB termination, IL-6, IL-8, and RI were significantly higher in group A (IL-6, 397.5 ± 80.6 pg/mL; IL-8, 26.99 ± 6.57 ng/mL; RI, 1.87 ± 0.31) than in group B (IL-6, 316.5 ± 73.9 pg/mL, p <0.05; IL-8, 17.21 ± 3.12 ng/mL, p < 0.01; RI, 1.57 ± 0.24, p < 0.05) although nitrate + nitrite (31.8 ± 4.1 μmol/L) and %NO2-Tyr (1.15% ± 0.20%) were significantly lower in group A than in group B (nitrate + nitrite, 50.2 ± 5.0 μmol/L, p < 0.01; %NO2-Tyr, 1.46% ± 0.21%, p < 0.01). Western immunoblot analysis from lung tissue of group A identified marked iNOS inhibition without inhibiting endothelial-constitutive NOS, and neutrophil accumulation in the lung specimens was significantly greater in group A (6.5 ± 0.7/alveoli) than in group B (4.4 ± 0.4/alveoli, p < 0.01). Conclusions. These results suggest that NO production from iNOS may be an adaptive response for attenuating the CPB-induced inflammatory response.