Avaliação dos efeitos do citrato de sildenafila na morfologia e no estresse oxidativo do córtex da glândula adrenal em animais espontaneamente hipertensos

Abstract

Essential hypertension is a major public health problem in the world. The most appropriate animal model for the study of this disease is the Spontaneously Hypertensive Rat (SHR). Hypertension is associated with the increase of reactive oxygen species, capable of combining with cellular components causing structural damage. Sildenafil citrate is an inhibitor of phosphodiesterase 5 that allows dilator stimulus prolongation by nitric oxide, helping to maintain vascular tone. The object of this study is the glomerular zone of the adrenal gland, because it is responsible for producing hormones that act on sodium reabsorption. All adrenal steroid hormones are produced by mitochondria, which suffers directly with the damage caused by oxidative stress. Therefore, the objective of this study was to evaluate the morphological changes and oxidative stress in hypertensive rats compared to hypertensive rats treated with sildenafil citrate. During the 30-day experiment 32 twenty-week-old rats, 16 SHR and 16 Wistar kyoto who received orogastric gavage daily were submitted to caudal artery plethysmography weekly. Initially, we evaluated a decrease in the thickness of the glomerular zone in the SHR group, which was reversed through cell proliferation in the treated group. Expression of SOD was elevated during hypertension and the treatment reduced its expression. However, the catalase enzyme did not present high levels of expression in the SHR group, which may have occurred due to the exhaustion of the protein. The detection of cytochrome C, as well as the pro-apoptotic protein Bax were higher in hypertensive patients, indicating the apoptotic process of the glomerular zone cells of this group. Treatment with sildenafil citrate had a protective effect, reducing the expression of these proteins. In the analysis of mitochondrial biogenesis, it was observed that sildenafil citrate stimulated the synthesis of PGC1α in treated animals. In ultrastructural evaluation of glomerular zone, cells were observed mitochondria with few cristae in SHR, while the cristae were tubular and well preserved in treated groups, besides having a greater number of secretory granules in the cytoplasm. These results indicate that sildenafil citrate may attenuate the effects of oxidative stress in the glomerular zone of adrenal on hypertension.