PMID- 15287858
OWN - NLM
STAT- MEDLINE
DCOM- 20050314
LR  - 20061115
IS  - 1478-3223 (Print)
IS  - 1478-3223 (Linking)
VI  - 24
IP  - 4
DP  - 2004 Aug
TI  - 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.
PG  - 345-53
AB  - BACKGROUND: The role of endothelial nitric oxide synthase 3 (NOS-3) in the 
      hyperdynamic circulation associated with cirrhosis is established but not that of 
      the neuronal (NOS-1) isoform. We therefore investigated aortic NOS-1 levels in 
      NOS-3 knock-out (KO) and wildtype (WT) mice and in hepatic arteries of patients. 
      METHODS: Mice rendered cirrhotic by bile duct ligation (BDL) were compared with 
      sham-operated controls. Hepatic arteries of cirrhotic patients were collected 
      during liver transplantation; donor vessels served as controls. mRNA levels were 
      quantified by real-time PCR, protein levels by Western blotting and NO production 
      by Nomega-nitro-L-arginine methyl ester inhibitable arginine-citrulline assay. 
      RESULTS: Aortae of NOS-3 KO mice exhibited higher NOS-1mRNA (5.6-fold, P < 0.004) 
      and protein levels (8.8-fold) compared with WT. NO production in aortae of NOS-3 
      KO mice was 52% compared with WT (P = 0.002). BDL increased NOS-1 mRNA (2.4-fold, 
      P = 0.01) and protein (7.1-fold) levels in aortae of WT, but no further in the 
      NOS-3 KO mice. Hepatic artery NOS-1 mRNA levels in cirrhotic patients were 
      markedly increased compared with controls (24.5-fold, P = 0.0007). CONCLUSIONS: 
      Increased NOS-1 mRNA and protein levels and partially maintained in vitro 
      NO-production in aortae of NOS-3 KO mice suggest that NOS-1 may partially 
      compensate for NOS-3 deficiency. BDL-induced increase in aortic NOS-1 mRNA and 
      protein levels hint that not only NOS-3, but also NOS-1 may be involved in the 
      regulation of systemic hyperdynamic circulation and portal hypertension. 
      Upregulation of NOS-1 mRNA levels in hepatic arteries of portal hypertensive 
      patients suggests possible clinical significance for these experimental findings.
CI  - Copyright Blackwell Munksgaard 2004
FAU - Biecker, Erwin
AU  - Biecker E
AD  - Department of Clinical Pharmacology, University of Berne, Murtenstrasse, 
      Switzerland.
FAU - Neef, Markus
AU  - Neef M
FAU - Sagesser, Hans
AU  - Sagesser H
FAU - Shaw, Sidney
AU  - Shaw S
FAU - Koshy, Abraham
AU  - Koshy A
FAU - Reichen, Jurg
AU  - Reichen J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.13.39 (NOS1 protein, human)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos1 protein, mouse)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Aorta/enzymology
MH  - Blotting, Western
MH  - Enzyme Activation
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Hypertension, Portal/metabolism/physiopathology
MH  - Liver Cirrhosis/metabolism/*physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/*genetics/*metabolism
MH  - Nitric Oxide Synthase/*genetics/*metabolism
MH  - Nitric Oxide Synthase Type I
MH  - Nitric Oxide Synthase Type II
MH  - Nitric Oxide Synthase Type III
MH  - RNA, Messenger/analysis
EDAT- 2004/08/04 05:00
MHDA- 2005/03/15 09:00
CRDT- 2004/08/04 05:00
PHST- 2004/08/04 05:00 [pubmed]
PHST- 2005/03/15 09:00 [medline]
PHST- 2004/08/04 05:00 [entrez]
AID - LIV933 [pii]
AID - 10.1111/j.1478-3231.2004.0933.x [doi]
PST - ppublish
SO  - Liver Int. 2004 Aug;24(4):345-53. doi: 10.1111/j.1478-3231.2004.0933.x.