Abstract:
BACKGROUND:Arterial vasodilatation, which is a major factor in the pathogenesis of the hyperkinetic circulatory state and portal hypertension in cirrhosis, is due to arterial nitric oxide (NO) overproduction secondary to endothelial NO synthase (eNOS) and inducible NOS (iNOS) upregulation. However, in cirrhosis, the respective roles of eNOS and iNOS isoforms in NO overproduction are still unknown and the effect of iNOS modulation on eNOS activity and expression has not been evaluated in the systemic or splanchnic vessels. The aim of this study was to evaluate the effects of modulating aortic and superior mesenteric arteries (SMA) iNOS on arterial eNOS activity and expression in rats with cirrhosis. METHODS:eNOS and iNOS protein expression and eNOS activity (assessed by its phosphorylation at serine 1177) were measured in the aortas and SMA in untreated and treated cirrhotic rats with lipopolysaccharide (LPS), N-iminoethyl-L-lysine (L-NIL), a selective iNOS inhibitor, and LPS plus L-NIL. RESULTS:LPS administration significantly increased eNOS and iNOS protein expression and eNOS activity in the aortas of both sham-operated and cirrhotic rats. However, in SMA, LPS administration induced a decrease in eNOS protein expression and activity and an increase in iNOS protein expression. CONCLUSION:The results of this study may explain the worsening of the hyperdynamic state in cirrhosis during septic shock by direct LPS-induced eNOS activation in large systemic vessels, and its inhibition in concomitant small splanchnic vasculature by iNOS synthesized NO.
journal_name
J Gastroenterol Hepatoljournal_title
Journal of gastroenterology and hepatologyauthors
Malyshev E,Tazi KA,Moreau R,Lebrec Ddoi
10.1111/j.1440-1746.2006.04608.xsubject
Has Abstractpub_date
2007-12-01 00:00:00pages
2195-201issue
12eissn
0815-9319issn
1440-1746pii
JGH4608journal_volume
22pub_type
杂志文章abstract:BACKGROUND AND AIM:To evaluate the optimal dosage of rabeprazole for proton-pump inhibitor (PPI) testing of gastroesophageal reflux disease (GERD) and to test the influence of cytochrome P450 (CYP) 2C19 polymorphism in a population with a high prevalence of people who metabolize PPI poorly. METHODS:In this randomized,...
journal_title:Journal of gastroenterology and hepatology
pub_type: 杂志文章,随机对照试验
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journal_title:Journal of gastroenterology and hepatology
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doi:10.1111/jgh.12270
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doi:10.1046/j.1440-1746.2001.02645.x
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of gastroenterology and hepatology
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pub_type: 杂志文章,评审
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journal_title:Journal of gastroenterology and hepatology
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