Nitric oxide decreases eicosanoid production via activation of guanylyl cyclase and polyADP-ribose synthase in endotoxin-stimulated whole blood, kidney and heart

Endotoksine in vivo veya in vitro maruziyet çeşitli hücre tiplerinde indüklenebilir nitrik oksit (NO) sentaz (iNOS), guanilil siklaz (GS), siklo-oksijenaz (COX) ve poli-ADP-riboz senlaz (PARS) 'yi aktive etmektedir. Bu çalışmanın amacı, tam kan, böbrek ve kalp kültüründe, İNOS kaynaklı NO 'nun GS veya PARS enzimlerini aktive ederek COX ile etkileşip etkileşmediğini araştırmaktadır. Endotoksin, tam kan ve dokularda lipit peroksidasyonu üzerinde bir etki oluşturmaksızın, nitrit düzeylerinde artmaya neden olmuştur. Endotoksin ile kan ve dokularda artan nitrit oluşumu aminoguanidin (İNOS inhibitörü), metilen mavisi (GS inhibitörü), indometazin (COXinhibitörü) veya 3-aminobenzamit (PARS inhibitörü) ile azalırken, indometazin dışında, bu maddeler bazı konsantrasyonlarında kanda nitrit oluşumunu artırmıştır. Endotoksin kan ve böbrekle tromboksan B2 (TxBJ oluşumunda bir azalmaya neden olmuştur. Endotoksinin kandaki bu etkisini aminoguanidin geri çevirmiştir. Endotoksin ile böbrekte oluşan TxB2 düzeyleri indometazin ile daha da azalmıştr. Bu bulgular, GS, COXveya PARS yollarının blokajının inhibisyonun derecesi ve doku tipine bağlı olarak nitrit oluşumunu azalttığı, artırdığını veya değiştirmediğini düşündürmektedir. iNOS kaynaklı NO, GS veya PARS enzimlerini aktive ederek eikozanoit oluşumunu azaltabilir.

Endotoksin ile uyarılan tam kan, böbrek ve kalpte nitrik oksit guanilil siklaz ve poli-ADP-riboz sentazı aktive ederek eikozanoit oluşumunu azaltmaktadır

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 ofGC 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 ofGC, 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 ofGC or PARS enzymes.

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