PMID- 9361348
OWN - NLM
STAT- MEDLINE
DCOM- 19980106
LR  - 20190914
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 8
IP  - 5
DP  - 1997 Nov
TI  - Use of selective and nonselective nitric oxide synthase inhibitors in rat 
      endotoxemia: effects on hepatic morphology and function.
PG  - 368-72
AB  - Endotoxin has profound effects on nitric oxide (NO) production, and considerable 
      controversies exist as to whether these alterations are beneficial or 
      deleterious. Increased mortality has been reported from nonselective inhibition 
      of NO synthase. Results from selective inhibition of the inducible isoform (iNOS) 
      appear largely positive. In a model of rat endotoxemia we have compared the early 
      effects on hepatic morphology and function of selective and nonselective NO 
      inhibition. Two hours after endotoxin injection (5 mg/kg intraportally) the rats 
      were treated with either the selective iNOS inhibitor aminoethyl isothiourea 
      (AE-ITU, 10 mg/kg), the nonselective NOS inhibitor NG-nitro-L-arginine methyl 
      ester (L-NAME, 10 mg/kg), or normal saline. The animals were observed for another 
      hour. Using an immunohistochemical method, induction of iNOS was demonstrated in 
      various tissues in all slices examined. No unequivocal benefit from NO inhibition 
      was noted. Electron microscopic examination revealed widespread alterations of 
      liver morphology, without obvious differences between the groups. Liver function, 
      as assessed by ketone body ratio, hepatic venous acid base values, and bile 
      production, was generally more adversely affected after NO inhibition. Even with 
      the iNOS selective inhibitor AE-ITU no benefit was noted. We conclude that during 
      the early phases of endotoxemia therapeutic reduction of NO production has no 
      positive effects on liver function or morphology.
FAU - Gundersen, Y
AU  - Gundersen Y
AD  - Institute for Surgical Research, Klinikum Grosshadern, University of Munich, 
      Germany.
FAU - Corso, C O
AU  - Corso CO
FAU - Leiderer, R
AU  - Leiderer R
FAU - Dorger, M
AU  - Dorger M
FAU - Lilleaasen, P
AU  - Lilleaasen P
FAU - Aasen, A O
AU  - Aasen AO
FAU - Messmer, K
AU  - Messmer K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ketone Bodies)
RN  - 151-16-6 (beta-Aminoethyl Isothiourea)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Acid-Base Equilibrium/drug effects
MH  - Animals
MH  - Bile/drug effects/physiology
MH  - Endotoxemia/*drug therapy/pathology/physiopathology
MH  - Enzyme Inhibitors/*pharmacology
MH  - Hemodynamics/drug effects
MH  - Ketone Bodies/blood
MH  - Liver/*drug effects/pathology/physiopathology
MH  - Male
MH  - Microscopy, Electron
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - beta-Aminoethyl Isothiourea/*pharmacology
EDAT- 1997/11/15 00:00
MHDA- 1997/11/15 00:01
CRDT- 1997/11/15 00:00
PHST- 1997/11/15 00:00 [pubmed]
PHST- 1997/11/15 00:01 [medline]
PHST- 1997/11/15 00:00 [entrez]
AID - 10.1097/00024382-199711000-00009 [doi]
PST - ppublish
SO  - Shock. 1997 Nov;8(5):368-72. doi: 10.1097/00024382-199711000-00009.