Efeito da carboximetil-glucana extraída da saccharomyces cerevisiae na função cardíaca e vascular de ratos

• Autor(a) principal: Vieira, Renata Layne Paixão
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
• Texto Completo: https://repositorio.ufpb.br/jspui/handle/123456789/12302
• topic: β-D-glucana; Saccharomyces cerevisae; Carboximetil-glucana; Reatividade vascular; Efeito inotrópico negativo; Infarto; CNPQ::CIENCIAS DA SAUDE::NUTRICAO

Carboxymethyl-glucan (CM-G) is a derivative obtained from (1→3) (1→6) β-D-glucan of Saccharomyces cerevisiae, characterized as being a biological response modifier, presenting antioxidant action, antiplatelet agent and hypolipidemic. These properties point to the potential of this derivative as protector of the cardiovascular system, however, research in this field is still scarce. The aim of this work was to investigate the role of CM-G on vascular reactivity, contractility of atrial and ventricular cardiomyocytes, and prevention of cardiac damage in an acute myocardial infarction (AMI) animal model. All the protocols developed were approved by the Ethical Committee on the Use of Animals (CEUA) of the UFPB under opinion nº 006/2016. Initially, the direct effect of CM-G on vascular reactivity, atrial and transient calcium contractility in ventricular cardiomyocytes was studied. Subsequently, experiments were performed on healthy animals, which were orally treated with CM-G at the dose of 50 mg / kg, daily for 21 days, compared to a control group. Experiments were then performed using an isoproterenol-induced animal model of AMI, in which, on the 20th and 21st days of the experiment, 85 mg / kg / day of isoproterenol was administered subcutaneously. On the 22nd day, 48 hours after the administration of the first dose of isoproterenol, the experimental tests were performed. CM-G induced a more pronounced concentration-dependent relaxing effect in vessels with functional endothelium (Emax=69.13 + 8.18%) compared to those without endothelium (Emax = 35.26 + 5.86%, p<0.05). The efficacy of CM-G-induced endothelium-dependent relaxation was significantly reduced in the pre-incubated rings with L-NAME (Emax = 30.91 ± 3.66%) or ODQ (Emax = 19.57 ± 4.08%) or carboxy-PTIO (Emax = 21.19 ± 3.42%) compared to the control (Emax = 69.13 + 8.18%, p<0.05). Treatment with CM-G promoted a reduction in contraction potency (pD2=7.103 + 0.06, Emax = 111.55 + 1.99%) in response to increasing concentrations of PHE when compared to the control group (pD2 = 6, 85 + 0.09, n = 8, p <0.05, Emax = 150.9 + 3.67%). ACH-induced relaxation had its efficacy increased in the aortic rings of the CM-G group (pD2 = 5.56 + 0.14 and Emax =90.10 + 3.71%, n =11) compared to the control group (PD2= 4.18 + 0.35, n =9, Emax = 69.87 + 4.27%, p <0.05). A negative inotropic effect was observed in the left atrium isolated from rats induced by CM-G, which was associated with a significant reduction of the maximum effectiveness of CaCl2 in increasing atrial contractility (Emax = 100% CM-G vs 73.41% CaCl2, P <0.05, n=5). This effect was accompanied by the reduction in intracellular Ca 2+ transient in ventricular cardiomyocytes of rats, both directly and after supplementation. There was no evidence of cardiac damage in an animal model of AMI caused by isoproterenol, when ST segment height and heart mass index were evaluated. The results of this study are unprecedented in demonstrating that CM-G induces relaxation in the aorta of rats with endothelium participation, increasing the synthesis and / or bioavailability of NO by NOS/NO/sCG pathway. In addition, it acts on the myocardium, inducing negative inotropic effect, through the modulation of Ca2+ handling. These findings provide new evidence pointing to the beneficial effects of CM-G on the cardiovascular system. Keywords: β-D-glucan, Saccharomyces cerevisae, carboxymethyl-glucan, vascular reactivity, negative inotropic effect, infarction.