Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/197252
Type: Artigo de periódico
Title: Hepatic Morphological Alterations, Glycogen Content And Cytochrome P450 Activities In Rats Treated Chronically With N(omega)-nitro-l-arginine Methyl Ester (l-name).
Author: Tarsitano, Christiane Aparecida Badin
Paffaro, Valdemar A
Pauli, José Rodrigo
da Silva, Gustavo Henrique
Saad, Mario J
Salgado, Ione
da Cruz-Höfling, Maria Alice
Hyslop, Stephen
Abstract: Chronic 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.
Subject: Angiotensin Ii Type 1 Receptor Blockers
Angiotensin-converting Enzyme Inhibitors
Animals
Chronic Disease
Cytochrome P-450 Enzyme System
Enalapril
Enzyme Activation
Enzyme Inhibitors
Fasting
Glucose
Glycogen
Glycogen Synthase Kinase 3
Hypertension
Hypertrophy
Liver
Liver Cirrhosis
Losartan
Male
Ng-nitroarginine Methyl Ester
Nitric Oxide
Peptidyl-dipeptidase A
Phosphorylation
Proto-oncogene Proteins C-akt
Rats
Rats, Wistar
Renin-angiotensin System
Rights: fechado
Identifier DOI: 10.1007/s00441-007-0411-9
Address: http://www.ncbi.nlm.nih.gov/pubmed/17436021
Date Issue: 2007
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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