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, CAB
dc.creatorPaffaro, VA
dc.creatorPauli, JR
dc.creatorda Silva, GH
dc.creatorSaad, MJ
dc.creatorSalgado, I
dc.creatorda Cruz-Hofling, MA
dc.creatorHyslop, S
dc.date2007
dc.dateJUL
dc.date2014-11-19T00:42:08Z
dc.date2015-11-26T17:00:07Z
dc.date2014-11-19T00:42:08Z
dc.date2015-11-26T17:00:07Z
dc.date.accessioned2018-03-28T23:47:53Z
dc.date.available2018-03-28T23:47:53Z
dc.identifierCell And Tissue Research. Springer, v. 329, n. 1, n. 45, n. 58, 2007.
dc.identifier0302-766X
dc.identifierWOS:000246178400005
dc.identifier10.1007/s00441-007-0411-9
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/68256
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/68256
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/68256
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1278385
dc.descriptionChronic treatment of rats with N-omega stop-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.description1
dc.description45
dc.description58
dc.languageen
dc.publisherSpringer
dc.publisherNew York
dc.publisherEUA
dc.relationCell And Tissue Research
dc.relationCell Tissue Res.
dc.rightsfechado
dc.rightshttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.sourceWeb of Science
dc.subjectcytochrome P450
dc.subjectglycogen
dc.subjecthypertension
dc.subjectliver
dc.subjectnitric oxide inhibition
dc.subjectrat (Wistar, male)
dc.subjectvascular hypertrophy
dc.subjectLong-term Blockade
dc.subjectOxide Synthase Inhibitor
dc.subjectAngiotensin-ii
dc.subjectDown-regulation
dc.subjectInsulin-resistance
dc.subjectGene-expression
dc.subjectInflammatory Cytokines
dc.subjectRenal-insufficiency
dc.subjectCardiac-hypertrophy
dc.subjectStructural-changes
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


Este ítem pertenece a la siguiente institución