Inclusão do ácido fítico em lipossoma potencializa seu efeito cardioprotetor na hipertensão arterial sistêmica em ratos

• Ano de defesa: 2019
• Autor(a) principal: Feitosa, Maraísa Bezerra de Jesus
• Orientador(a): Santos, Sandra Lauton
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Ciências da Saúde
• Palavras-chave em Português: Hipertensão; Ácido fítico; Metaloproteinases da matriz; Antioxidantes; Hipertrofia ventricular; Metaloproteases; Hexafosfato de inositol; Lipossoma; MMPs
• Palavras-chave em Inglês: Antioxidants; Inositol hexaphosphate; Hypertension; Left ventricular hypertrophy; Metalloproteinases; Liposome
• Área do conhecimento CNPq: CIENCIAS DA SAUDE
• Link de acesso: http://ri.ufs.br/jspui/handle/riufs/13075

Cardiovascular diseases represent the leading cause of death in Brazil, and the arterial hypertension (AH) is one of the main risk factors. Several models mimetizing AH pathophysiology have been used, as wellas, spontaneously hypertensive rats (SHR). Present multifactorial etiopathogenic involvement, whose endothelial dysfunction is the central mechanism. Knowing that nitric oxide (NO) has a protective effect on AH and that increasing the production of reactive oxygen species (ROS) may reduce its availability, nutraceutics have been used as a complement to control this pathology. One is inositol and its phosphorylated forms such as phytic acid (FA), which sequestered ROS may increase the bioavailability of NO. Thus, the present study aimed to investigate the effect of phytic acid treatment on the cardiovascular function of spontaneously hypertensive animals. Male Wistar rats (CTR) and SHR (SHR Vehicle), aging 16 to 18 weeks, weighing between 300 and 450g were used. The SHR were treated with free phytic acid (SHR Free/FA) or phytic acid included in the liposome (SHR Lipo/FA). In vivo electrocardiogram records were performed before and after treatments and heart rate (HR) reduction was observed on treated animals. Left ventricular developed pressure (LVDP) in the isolated heart of animals in the Langendorff perfusion system was evaluated. FA reduces pressure compared to vehicle group. Heart mass index was measured and normalized by the body mass of each animal at the end of the study. Heart mass was reduced in both treatments with FA when compared to the vehicle group. The expression of MMP - 2 and - 9 in the ventricles (LV) was evaluated by Western blot. MMP-2 decreased only in the liposome-treated group and MMP-9 decreased in both cases compared to the vehicle group. In selected rings of the superior mesenteric artery, phenylephrine (Phe)contraction curves, acetylcholine (ACh) and sodium nitroprusside (SNP) relaxation were constructed. The participation of NO production (with L-NAME) and prostacyclin (indomethacin) in vasodilation was also evaluated. The response to Phe was increased on intact endothelium mesenteric rings but there was no difference on the mesenteric rings without endothelium. In SHR Lipo/FA or ACh-induced relaxation groups were potentiated compared to SHR Livre/FA and SHR Vehicle. In the relaxation curve induced by NPS, there was no difference between the groups. Were quantified the enzymatic activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and reductase (GR), besides lipoperoxidation (TBARS) and protein oxidation (sulfhydryl group - SH) in LV. In the aorta, there was no difference in SOD, but in cardiac tissue both effects with AF increased this marker when compared to the vehicle group. SHR Lipo/FA presented incresead CAT activity in aorta while both kinds of treatment increased this marker on heart tissues Cardiac GPx just increased um liposome group treatment when compared to the vehicle. Both treatments were able to increase GR activity when compared to the vehicle group. There was a reduction in TBARS in both groups with FA compared to the vehicle group. The -SH groups increased only in SHR Lipo/FA group relative to the vehicle Thus, we can define how FA decreases HR and LVDP, and can modulate the expression of MMPs in SHR, in addition to promoting endothelium-dependent relaxation for ACh in rat mesenteric artery, an effect dependent on NO that is enhanced in inclusion. Regarding redox status, AF promotes reduction of lipid peroxidation and protects against protein oxidation, improves the activity of antioxidant enzymes, being that, inclusion in the liposome enhances the enzymatic activity of CAT in the aorta and, GPx and GR in heart, when used compared to a free form. Taken together, our data suggest treatment with AF protected the heart from cardiovascular damage promoted by hypertension and that FA inclusion in liposome potentiating these effects.