Hepatic Morphological Alterations, Glycogen Content And Cytochrome P450 Activities In Rats Treated Chronically With N(omega)-nitro-l-arginine Methyl Ester (l-name).

dc.creatorTarsitano, Christiane Aparecida Badin
dc.creatorPaffaro, Valdemar A
dc.creatorPauli, José Rodrigo
dc.creatorda Silva, Gustavo Henrique
dc.creatorSaad, Mario J
dc.creatorSalgado, Ione
dc.creatorda Cruz-Höfling, Maria Alice
dc.creatorHyslop, Stephen
dc.date2007-Jul
dc.date2015-11-27T13:10:01Z
dc.date2015-11-27T13:10:01Z
dc.date.accessioned2018-03-29T01:04:40Z
dc.date.available2018-03-29T01:04:40Z
dc.identifierCell And Tissue Research. v. 329, n. 1, p. 45-58, 2007-Jul.
dc.identifier0302-766X
dc.identifier10.1007/s00441-007-0411-9
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/17436021
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/197252
dc.identifier17436021
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1297485
dc.descriptionChronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined the influence of L-NAME on rat liver morphology, on hepatic glycogen, cholesterol, and triglyceride content, and on the activities of the cytochrome P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks, and their livers were then removed for analysis. Enzymatic induction was produced by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated blood pressure; this was reversed by concomitant treatment with enalapril (ACE inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused vascular hypertrophy in hepatic arteries, with perivascular and interstitial fibrosis involving collagen deposition. Hepatic glycogen content also significantly increased. L-NAME did not affect fasting glucose levels but significantly reduced insulin levels and increased the insulin sensitivity of rats, based on an intraperitoneal glucose tolerance test. Immunoblotting experiments indicated enhanced phosphorylation of protein kinase B and of glycogen synthase kinase 3. All these changes were reversed by concomitant treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol or triglyceride content or on the basal or drug-induced activities and protein expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO biosynthesis produced hepatic morphological alterations and changes in glycogen metabolism mediated by the renin-angiotensin system. The increase in hepatic glycogen content probably resulted from enhanced glycogen synthase activity following the inhibition of glycogen synthase kinase 3 by phosphorylation.
dc.description329
dc.description45-58
dc.languageeng
dc.relationCell And Tissue Research
dc.relationCell Tissue Res.
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAngiotensin Ii Type 1 Receptor Blockers
dc.subjectAngiotensin-converting Enzyme Inhibitors
dc.subjectAnimals
dc.subjectChronic Disease
dc.subjectCytochrome P-450 Enzyme System
dc.subjectEnalapril
dc.subjectEnzyme Activation
dc.subjectEnzyme Inhibitors
dc.subjectFasting
dc.subjectGlucose
dc.subjectGlycogen
dc.subjectGlycogen Synthase Kinase 3
dc.subjectHypertension
dc.subjectHypertrophy
dc.subjectLiver
dc.subjectLiver Cirrhosis
dc.subjectLosartan
dc.subjectMale
dc.subjectNg-nitroarginine Methyl Ester
dc.subjectNitric Oxide
dc.subjectPeptidyl-dipeptidase A
dc.subjectPhosphorylation
dc.subjectProto-oncogene Proteins C-akt
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectRenin-angiotensin System
dc.titleHepatic Morphological Alterations, Glycogen Content And Cytochrome P450 Activities In Rats Treated Chronically With N(omega)-nitro-l-arginine Methyl Ester (l-name).
dc.typeArtículos de revistas


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