Efeito dos inibidores do sistema renina angiotensina aldosterona sobre os marcadores de estresse oxidativo, enzimas antioxidantes e apoptose na artéria carótida de ratos induzidos ao modelo de hipertensão 2R1C

Abstract

Oxidative stress (OS) participates in the pathophysiology of renovascular hypertension (RH) and can lead to cell death by activating the intrinsic apoptosis pathway. We aimed to evaluate the morphofunctional changes in the common carotid artery of Wistar rats induced in the HR model after treatment with Losartan, Enalapril and Spironolactone. Male Wistar rats were induced to HR by left renal artery clipping or sham surgery (SHAM) and treated with losartan (10mg/kg/day) or enalapril (10mg/kg/day) or spironolactone (25mg/kg/day) or vehicle for 4 weeks, via gavage. Euthanasia occurred in the 8th week, the end of the experiment. Systolic blood pressure (SBP) was measured using the non-invasive method of caudal artery plethysmography. Plasma aldosterone levels were determined by ELISA. Bax, Bcl-2, cytochrome c, caspase 3, gp91(phox), and GPX-1 were examined by immunohistochemistry. Malondialdehyde (MDA) content and superoxide dismutase, catalase (CAT) and glutathione peroxidase (GPx) activities were detected by enzymatic assay. The ultrastructure of the carotid artery was observed by transmission electron microscopy. All treatments, losartan, enalapril and spironolactone, significantly reduced SBP, gp91(phox) and apoptotic markers, except caspase 3. Enalapril increased GPX-1 expression. The above results collectively suggested that spironolactone, losartan and enalapril brought beneficial effects by promoting experimental HR-induced changes in SBP and apoptosis markers.