Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock‐out mice and is elevated in murine and human cirrhosis

• DOI: 10.1111/j.1478-3231.2004.0933.x
• Publication Date: 2004-07-30T12:56:46Z
• Authors: Erwin Biecker; Markus Neef; Hans Sägesser; Sidney Shaw; Abraham Koshy; Jürg Reichen
• Keywords: Endothelial NOS; Hyperdynamic circulation

Abstract: Background: The role of endothelial nitric oxide synthase 3 (NOS‐3) in the hyperdynamic circulation associated with cirrhosis is established but not that neuronal (NOS‐1) isoform. We therefore investigated aortic NOS‐1 levels NOS‐3 knock‐out (KO) and wildtype (WT) mice hepatic arteries patients. Methods: Mice rendered cirrhotic by bile duct ligation (BDL) were compared sham‐operated controls. Hepatic patients collected during liver transplantation; donor vessels served as mRNA quantified real‐time PCR, protein Western blotting NO production N ω ‐nitro‐ l ‐arginine methyl ester inhibitable arginine–citrulline assay. Results: Aortae KO exhibited higher NOS‐1mRNA (5.6‐fold, P <0.004) (8.8‐fold) WT. aortae was 52% WT ( =0.002). BDL increased (2.4‐fold, =0.01) (7.1‐fold) WT, no further mice. artery markedly controls (24.5‐fold, =0.0007). Conclusions: Increased partially maintained vitro NO‐production suggest may compensate for deficiency. BDL‐induced increase hint only NOS‐3, also be involved regulation systemic portal hypertension. Upregulation hypertensive suggests possible clinical significance these experimental findings.