A carboximetil-glucana exerce ação anti-hipertensiva, modulação positiva da função vascular e atividade antiplaquetária em ratos espontaneamente hipertensos

Abstract

Yeast β-D-Glucans are polysaccharides consisting of a central linear skeleton of glucose units linked at the β (1-3) position and side chains joined by β (1-6) linkages. These polymers are important biological response modifiers and have several biological effects beneficial to health. Therefore, there is great interest in its derivatives, especially in the carboxymethylated form, which demonstrates antioxidant, immunostimulant, antiplatelet, and vascular function modulating action. However, its action on cardiovascular function is still poorly understood, mainly in hypertension. Therefore, this study aimed to investigate the effects of Carboxymethyl-glucan (CMG) from Saccharomyces cerevisiae on blood pressure, vascular function, autonomic modulation, platelet aggregation, and oxidative stress in spontaneously hypertensive rats (SHR). All experimental protocols were approved by the UFPB's Ethics Committee on Animal Use (CEUA 087/2017). Male SHR and their normotensive Wistar Kyoto (WKY) controls were assigned to groups (n=8): WKY control (WKY CT); WKY CMG 60 mg/kg; SHR control (SHR CT); SHR CMG 20 mg/kg and SHR CMG 60 mg/kg. The animals were treated for four weeks at doses of 20 and 60 mg/kg orally, and the controls received saline. At the end of treatment, weight gain, biochemical parameters, blood pressure levels, baroreflex sensitivity, and sympathetic tone participation were evaluated. Then, the animals were euthanized for vascular reactivity tests, platelet aggregation evaluation, histological, morphometric, and antioxidant capacity analyses. The results showed that CMG treatment decreased the weight gain in SHR CMG 60 mg/kg, and changed lipid profile and renal function, with a reduction in urea. Only in the SHR CMG 60 mg/kg group was observed a significant reduction in mean arterial pressure. However, the two doses tested promoted a reduction in systolic and diastolic blood pressure, without changing heart rate in the SHR groups, and also decreased cardiac hypertrophy.Modulation in baroreflex gain was observed, promoting improved response in SHR CMG 60 mg/kg animals, and decreased sympathetic tone involvement in this group. As for vascular function, improvement in the endothelium dependent vasorelaxant response assessed by acetylcholine (ACh) was verified in SHR CMG 20 mg/kg and SHR CMG 60 mg/kg groups. In the vasorelaxation induced by sodium nitroprusside (SPN), an improved response was observed in the WKY CMG 60 mg/kg animals. Platelet aggregation studies demonstrated lower platelet aggregation in the SHR CMG 60 mg/kg group compared to the SHR CT, when induced by adenosine diphosphate (ADP). Oxidative stress analyses showed that although SHR CT animals had significantly higher levels of reactive oxygen species (ROS) compared to WKY CT, CMG was not able to promote ROS reduction. These findings suggest that CMG improves vascular function in SHR animals, demonstrating antihypertensive action through baroreflex via negative modulation of sympathetic tone, and has platelet antiaggregant property. Thus, CMG presents itself as a potential strategy for the management of arterial hypertension.