Abstract Exposure to endotoxin in vivo or in vitro activates nitric oxide (NO) by inducible NO synthase (iNOS) as well as guanylyl cyclase (GC), cyclo-oxygenase (COX) and polyADP-ribose synthase (PARS) in several cell types. The aim of this study was to invesigate whether iNOS-derived NO could interact with COX via activation of GC or PARS enzymes in whole blood, kidney and heart culture. Endotoxin caused increased levels of nitrite without any effect on lipid peroxidation in whole blood and tissues. The endotoxin-induced increase in nitrite production was decreased by aminoguanidine (iNOS inhibitor), methylene blue (GC inhibitor), indomethacin (COX inhibitor) or 3-aminobenzamide (PARS inhibitor) in blood and tissues while certain concentrations of the agents, except for indomethacin, also increased nitrite production in blood. Endotoxin caused a decrease in thromoboxane B2 (TxB2) production in blood and kidney. Aminoguanidine reversed the effect of endotoxin in blood. The endotoxin-induced levels of TxB2 were further decreased by indomethacin in kidney. These results suggest that blockade of GC, COX or PARS pathways decreases, increases or does not change nitrite production depending on the degree of inhibition and tissue type. iNOS-derived NO may decrease eicosanoid production via activation of GC or PARS enzymes. Özet Endotoksine in vivo veya in vitro maruziyet çesitli hücre tiplerinde indüklenebilir nitrik oksit (NO) sentaz (iNOS), guanilil siklaz (GS), siklo-oksijenaz (COX) ve poli-ADP-riboz sentaz (PARS)’yi aktive etmektedir. Bu çalismanin amaci, tam kan, böbrek ve kalp kültüründe, iNOS kaynakli NO’nun GS veya PARS enzimlerini aktive ederek COX ile etkilesip etkilesmedigini arastirmaktadir. Endotoksin, tam kan ve dokularda lipit peroksidasyonu üzerinde bir etki olusturmaksizin, nitrit düzeylerinde artmaya neden olmustur. Endotoksin ile kan ve dokularda artan nitrit olusumu aminoguanidin (iNOS inhibitörü), metilen mavisi (GS inhibitörü), indometazin (COX inhibitörü) veya 3-aminobenzamit (PARS inhibitörü) ile azalirken, indometazin disinda, bu maddeler bazi konsantrasyonlarinda kanda nitrit olusumunu artirmistir. Endotoksin kan ve böbrekte tromboksan B2 (TxB2) olusumunda bir azalmaya neden olmustur. Endotoksinin kandaki bu etkisini aminoguanidin geri çevirmistir. Endotoksin ile böbrekte olusan TxB2 düzeyleri indometazin ile daha da azalmistr. Bu bulgular, GS, COX veya PARS yollarinin blokajinin inhibisyonun derecesi ve doku tipine bagli olarak nitrit olusumunu azalttigi, artirdigini veya degistirmedigini düsündürmektedir. iNOS kaynakli NO, GS veya PARS enzimlerini aktive ederek eikozanoit olusumunu azaltabilir.

Keywords: Endotoxin, nitric oxide, mice, blood, kidney, heart