EFEITOS DO TRATAMENTO COMBINADO COM L-ARGININA E BENAZEPRIL EM ANÉIS DE AORTA DE RATOS COM HIPERTENSÃO RENOVASCULAR

Abstract

Systemic arterial hypertension is related to a high risk of developing cardiovascular diseases, as it leads to vascular changes and endothelial dysfunction. In this article we investigate treatment with benazepril and L-arginine, alone and in combination, on Systolic Blood Pressure (SBP) and vascular reactivity in aortic rings. Hypertension was induced in male Wistar rats by severing the left renal artery. The animals were divided into groups:Sham, 2-kidney 1 clip (2K1C), hypertension, 2K1C + L-arginine (L-ARG), 2K1C + Benazepril (Ben) and 2K1C + L-arginine + Benazepril (L-arg + Ben), the treatments were for 21 days.For 4 weeks, BP was monitored and endothelium-dependent and endothelium-independent vasoconstriction and relaxation were assessed in aortic rings. L-arg + Bem reducedBP andcontractile response to phenylephrine and improved acetylcholine relaxation. Removal and incubation of the endothelium with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the L-arg + Ben group. We used an in situdetection assay of NO measured by the DAF-2 fluorescent probe. 2K1C hypertension reduced in situNO production when compared to the Sham group. However, the L-arg + Ben group showed higher NO production. The analysis ofthe fluorescence produced by Dihydroethide -DHE in the aorta artery revealed an increase in the production of ROS in 2K1C animals and that treatments with L-ARG, BEN and L-ARG+BEN were effective in reducing their normalized fluorescence values, correcting the increased production of ROS in arteries generated by 2K1C hypertension. In conclusion, combined L-arg + Ben was effective in lowering blood pressure and preventing endothelial dysfunction in the aortic rings of 2K1C hypertensive rats. The responsiblemechanisms seem to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress and an increase in nitric oxide production.