Validação da predição de um modelo para indução da aterosclerose e comprometimento hepato-renal em ratas Wistar

Abstract

Therapeutic approaches for the treatment of dyslipidemia and atherosclerosis have radically changed in recent decades. Part of this advance undeniably stems from basic biomedical research that has provided a better understanding and identification of new therapeutic targets. The aim of this work was to develop a model to induce atherogenesis and hepato-renal impairment in female Wistar rats. The following groups received the respective treatments for 60 days: control animals, non-ovariectomized rats that received an atherogenic diet (NEAD), ovariectomized rats that received an atherogenic diet (NOAD), non-ovariectomized rats that received an atherogenic diet and oral Nω-nitro-L-arginine methyl ester hydrochloride (LNAME; LEAD), and ovariectomized rats that received an atherogenic diet and oral L-NAME (LOAD). The atherogenic diet was composed of 64.4% standard diet, 0.5% cholesterol, 0.1% sodium cholate, 5% sucrose, 5% lard, 5% hydrogenated fat, and 20% egg powder. Animals in the NEAD, NOAD, LEAD, and LOAD groups also received methimazole (2mg/Kg) daily and cholecalciferol (700.000 U/Kg) each two days, divided in four injection intraperitoneal route. Urinary, biochemical, hemodynamic, and electrocardiographic parameters and renal function were assessed. Samples of the liver, heart, kidney, and arteries were collected to investigate redox status and perform histopathological analyses. All of the groups developed dyslipidemia and hepatic steatosis. Only the NEAD group developed arterial lesions that were compatible with fatty streaks. Renal function was significantly impaired in the LEAD and NOAD groups. These results indicate a viable alternative to induce atherogenesis and hepato-renal impairment in female rats.