PT - JOURNAL ARTICLE AU - YUKIO SUGA AU - YOKO TAKAHASHI AU - TSUTOMU SHIMADA AU - SHINYA YAMADA AU - ERIKO MORISHITA AU - HIDESAKU ASAKURA TI - Effect of NOS Inhibitors and Anticoagulants on Nitric Oxide Production in a Tissue-factor Induced Rat DIC Model AID - 10.21873/invivo.12468 DP - 2021 Jul 01 TA - In Vivo PG - 1999--2004 VI - 35 IP - 4 4099 - http://iv.iiarjournals.org/content/35/4/1999.short 4100 - http://iv.iiarjournals.org/content/35/4/1999.full SO - In Vivo2021 Jul 01; 35 AB - Background/Aim: We examined the mechanism of nitric oxide (NO) production in a tissue-factor (TF)-induced disseminated intravascular coagulation (DIC) model in rats, using inducible nitric oxide synthase (iNOS) inhibitor (L-NIL), endothelial nitric oxide synthase (eNOS) inhibitor (L-NAME), Factor Xa inhibitor (DX-9065a), and thrombin inhibitor argatroban. Materials and Methods: Experimental DIC was induced by sustained infusion of 3.75 U/kg TF for 4 h via the tail vein. We then investigated the effect of these four agents on TF-induced DIC. Results: Administration of L-NIL or L-NAME during induction of TF-induced DIC did not affect hemostatic markers, whereas elevated plasma levels of NO metabolites (NOX) were significantly suppressed by co-administration of L-NAME. A significant increase in eNOS-mRNA expression was observed in the TF-induced DIC model. Argatroban almost completely suppressed eNOS-mRNA expression. Conclusion: eNOS plays an important role in the NO production in the TF-induced DIC, and thrombin is a key stimulant of eNOS-mRNA expression in this model.