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Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with N(omega)-nitro-L-arginine methyl ester (L-NAME).
Cell Tissue Res. 2007 Jul; 329(1):45-58.CT

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.

Authors+Show Affiliations

Departamento de Farmacologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), CP 6111, 13083-970 Campinas, SP, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17436021

Citation

Tarsitano, Christiane Aparecida Badin, et al. "Hepatic Morphological Alterations, Glycogen Content and Cytochrome P450 Activities in Rats Treated Chronically With N(omega)-nitro-L-arginine Methyl Ester (L-NAME)." Cell and Tissue Research, vol. 329, no. 1, 2007, pp. 45-58.
Tarsitano CA, Paffaro VA, Pauli JR, et al. Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with N(omega)-nitro-L-arginine methyl ester (L-NAME). Cell Tissue Res. 2007;329(1):45-58.
Tarsitano, C. A., Paffaro, V. A., Pauli, J. R., da Silva, G. H., Saad, M. J., Salgado, I., da Cruz-Höfling, M. A., & Hyslop, S. (2007). Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with N(omega)-nitro-L-arginine methyl ester (L-NAME). Cell and Tissue Research, 329(1), 45-58.
Tarsitano CA, et al. Hepatic Morphological Alterations, Glycogen Content and Cytochrome P450 Activities in Rats Treated Chronically With N(omega)-nitro-L-arginine Methyl Ester (L-NAME). Cell Tissue Res. 2007;329(1):45-58. PubMed PMID: 17436021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with N(omega)-nitro-L-arginine methyl ester (L-NAME). AU - Tarsitano,Christiane Aparecida Badin, AU - Paffaro,Valdemar A,Jr AU - Pauli,José Rodrigo, AU - da Silva,Gustavo Henrique, AU - Saad,Mario J, AU - Salgado,Ione, AU - da Cruz-Höfling,Maria Alice, AU - Hyslop,Stephen, Y1 - 2007/04/14/ PY - 2006/06/23/received PY - 2007/03/02/accepted PY - 2007/4/17/pubmed PY - 2007/10/11/medline PY - 2007/4/17/entrez SP - 45 EP - 58 JF - Cell and tissue research JO - Cell Tissue Res VL - 329 IS - 1 N2 - 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. SN - 0302-766X UR - https://www.unboundmedicine.com/medline/citation/17436021/Hepatic_morphological_alterations_glycogen_content_and_cytochrome_P450_activities_in_rats_treated_chronically_with_N_omega__nitro_L_arginine_methyl_ester__L_NAME__ L2 - https://dx.doi.org/10.1007/s00441-007-0411-9 DB - PRIME DP - Unbound Medicine ER -