PMID- 9186843
OWN - NLM
STAT- MEDLINE
DCOM- 19970811
LR  - 20190817
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 26
IP  - 5
DP  - 1997 May
TI  - Induction of nitric oxide synthase II does not account for excess vascular nitric 
      oxide production in experimental cirrhosis.
PG  - 1120-7
AB  - BACKGROUND/AIMS: Excess production of nitric oxide (NO) reduces vasoconstriction 
      of cirrhotic rat aorta. Expression of the inducible nitric oxide synthase (NOS 
      II) in endothelial cells or vascular smooth muscle could account for this, as 
      described with endotoxin or lipopolysaccharide (LPS) treatment. Alternatively, 
      the endothelial NOS enzyme (NOS III) could be activated by an as-yet undescribed 
      mechanism. Here we describe a combined study of the basal release of NO and 
      quantitative measurement of the mRNA for NOS II and NOS III from thoracic aorta 
      of an animal model of cirrhosis. METHODS: Thoracic aortas of six normal, six 
      cirrhotic (secondary biliary cirrhosis) and six intra-peritoneal LPS-treated (15 
      mg/kg) rats were removed. Dissected aortic rings were precontracted with 
      norepinephrine (NE; 10(-6) M) and relaxed with acetylcholine (Ach; 10(-6) M) with 
      or without pre-incubation with the specific NOS inhibitor (L-NNA, 10(-5) M). 
      Total RNA was extracted from aorta, reverse transcribed (RT) and used in 
      polymerase chain reaction (PCR) amplification with primers specific for NOS II, 
      NOS III and beta-actin. PCR products were hybridized with fluorescein labelled 
      cDNA probes and the relative intensity on film was analyzed by densitometry. 
      RESULTS: Compared to normal, NE caused 32% less contraction in cirrhotic and 43% 
      less contraction in LPS-treated aortic rings. This response was corrected to 
      normal by L-NNA pre-incubation. All the contracted rings relaxed with Ach. NOS II 
      mRNA, was expressed only in LPS-treated aorta and not in aorta from normal and 
      cirrhotic rats. NOS III mRNA levels were the same in normal, cirrhotic and 
      LPS-treated rats: 1176 +/- 170, 1233 +/- 626 and 979 +/- 423, in arbitrary 
      densitometry units, respectively. CONCLUSIONS: NO is overproduced by aorta from 
      cirrhotic and LPS-treated rats. In LPS-treated rats this could result from 
      expression of NOS II, but this was not the case in the cirrhotic rat aorta. 
      Comparable amounts of NOS III mRNA suggest that, in cirrhosis, increased activity 
      of this enzyme and not increased NOS III expression is responsible for the 
      overproduction of NO.
FAU - Sogni, P
AU  - Sogni P
AD  - Dept. Medicine and Pharmacology, University of Sheffield, UK.
FAU - Smith, A P
AU  - Smith AP
FAU - Gadano, A
AU  - Gadano A
FAU - Lebrec, D
AU  - Lebrec D
FAU - Higenbottam, T W
AU  - Higenbottam TW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Isoenzymes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/*metabolism
MH  - Enzyme Induction
MH  - Isoenzymes/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Liver Cirrhosis, Experimental/*metabolism
MH  - Male
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase/genetics/*metabolism
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription, Genetic
MH  - Vasoconstriction
MH  - Vasodilation
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - S0168-8278(97)80121-3 [pii]
AID - 10.1016/s0168-8278(97)80121-3 [doi]
PST - ppublish
SO  - J Hepatol. 1997 May;26(5):1120-7. doi: 10.1016/s0168-8278(97)80121-3.