Efeitos da suplementação crônica de nitrato inorgânico sobre as alterações vasculares induzidas pelo envelhecimento em ratos

Abstract

Aging is associated with increased blood pressure (BP), endothelial dysfunction, and elevated oxidative stress, processes that can lead to cardiovascular diseases. Dietary supplementation with inorganic nitrate has been suggested as a strategy to enhance nitric oxide (NO) bioavailability, aiding in BP reduction and vascular protection in both experimental and clinical models. To evaluate the effects of chronic inorganic nitrate supplementation on BP, aerobic capacity, and vascular function in aged rats. Eighteen-month-old male and female Wistar rats were divided into four groups (n=6/group): Male Placebo (MP), Male Nitrate (MN), Female Placebo (FP), and Female Nitrate (FN). The supplementation consisted of sodium nitrate (1 mmol/kg/day) administered in drinking water for 12 weeks; the placebo group received sodium chloride (NaCl). The following parameters were assessed: body mass, food and water intake, fasting blood glucose, oral glucose tolerance test (OGTT), time to exhaustion, and maximal treadmill speed. Systolic (SBP) and diastolic (DBP) blood pressure were measured weekly using tail-cuff plethysmography. At the end of the study, aortic rings were analyzed for vascular reactivity, morphological assessment, and Western blot analysis, while blood samples were used to evaluate L-arginine transport, NOS activity in erythrocytes, and oxidative damage markers. Nitrate supplementation progressively reduced SBP and DBP in both sexes. No significant differences were observed in fasting blood glucose or OGTT between groups, although males exhibited a later peak glucose response compared to females. The MN and FN groups showed enhanced endothelium-dependent vasodilation but no changes in endothelium-independent relaxation or contractile response to phenylephrine compared to their respective controls. No differences were found in aortic structure or aerobic capacity. Nitrate supplementation increased L-arginine transport and NOS activity in erythrocytes while reducing plasma TBARS levels, suggesting lower systemic oxidative damage. However, lipid peroxidation and protein carbonylation in erythrocytes, as well as NOX4 and eNOS expression in aortic homogenates, remained unchanged between groups. In aged rats, chronic inorganic nitrate supplementation significantly reduced BP and improved endothelium-dependent vasodilation without altering vascular morphology or aerobic capacity. These findings reinforce the potential of nitrate as a therapeutic tool for mitigating endothelial dysfunction and hypertension in aging models.