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 x kg(-1) x min(-1), 34 degrees 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 micromol/L) and %NO2-Tyr (1.15%+/-0.20%) were significantly lower in group A than in group B (nitrate + nitrite, 50.2+/-5.0 micromol/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.
Hayashi
Y
Y
Department of Surgery, Course of Interventional Medicine, Osaka University Graduate School of Medicine, Suita City, Japan.
Sawa
Y
Y
Fukuyama
N
N
Nakazawa
H
H
Matsuda
H
H
D000818:Animals; D002315:Cardiopulmonary Bypass; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D004790:Enzyme Induction / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*
D006146:Guanidines; D015850:Interleukin-6; D016209:Interleukin-8; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine