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Use of selective and nonselective nitric oxide synthase inhibitors in rat endotoxemia: effects on hepatic morphology and function.
- Source :
-
Shock (Augusta, Ga.) [Shock] 1997 Nov; Vol. 8 (5), pp. 368-72. - Publication Year :
- 1997
-
Abstract
- 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.
- Subjects :
- Acid-Base Equilibrium drug effects
Animals
Bile drug effects
Bile physiology
Endotoxemia pathology
Endotoxemia physiopathology
Hemodynamics drug effects
Ketone Bodies blood
Liver pathology
Liver physiopathology
Male
Microscopy, Electron
NG-Nitroarginine Methyl Ester pharmacology
Rats
Rats, Sprague-Dawley
Endotoxemia drug therapy
Enzyme Inhibitors pharmacology
Liver drug effects
Nitric Oxide Synthase antagonists & inhibitors
beta-Aminoethyl Isothiourea pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1073-2322
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 9361348
- Full Text :
- https://doi.org/10.1097/00024382-199711000-00009