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Published on: July 29, 2021
Effect of NOS Inhibitors and Anticoagulants on Nitric Oxide Production in a Tissue-factor Induced Rat DIC Model
Yukio Suga1, Yoko Takahashi2, Tsutomu Shimada3
1Department of Clinical Pharmacy and Healthcare Science, Faculty of Pharmacy, Institute of Medical, Pharmaceutical & Health Science, Kanazawa University, Kanazawa, Japan; suga@staff.kanazawa-u.ac.jp.
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.
