Avaliação do efeito cardioprotetor exercido por nanoformulações produzidas a partir de dois extratos vegetais em ratos espontaneamente hipertensos

Abstract

Systemic arterial hypertension is a chronic disease characterized by elevated systolic blood pressure ≥ 140 mm Hg and diastolic blood pressure ≥ 90 mm Hg. It is a multifactorial condition that affects around 30% of the world's population, making it an important public health problem. Based on this context, the aim of this study was to evaluate the effects of two nanoformulations produced from plant species in the treatment of situations involving hypertension. In the first study, the oil of Athallea phalerata, popularly known as acurí, was extracted and characterized. Nanocapsules were prepared using the nanoprecipitation method and subsequently analyzed and characterized. In regard to animal experimentation, three experimental protocols were carried out using male spontaneously hypertensive rats (SHR). In the first protocol, anesthetized SHR rats had their carotid arteries cannulated to measure blood pressure. Subsequently, animals received different doses of acurí nanocapsules (1, 3 and 10 mg/kg), enalapril (5 mg/kg) or vehicle (0.9% saline solution; 100 µl per 100 g of body weight), thus allowing acute assessment of blood pressure. For the second experimental set, different groups of SHR rats received prolonged oral treatment (seven days), with the acurí nanocapsules (1, 3 and 10 mg/kg), enalapril (5 mg/kg) or vehicle (filtered water; 100 µl per 100 g body weight). On the eighth day of the experiment, animals were anesthetized and operated on, to allow blood pressure measurements via carotid artery for 35 minutes. For the third protocol, different groups of SHR rats had the left femoral artery cannulated and connected to an infusion pump, followed by the administration of L-NAME (7 mg/kg/min); methylene blue (150 nmol/kg/min) was continuously infused; a single dose of DDA (0.1 mg/kg); TEA 400 (µmol/kg); or acuri nanocapsules (3 mg/kg) were administered intraperitoneally; each animal received only one substance and after administration, blood pressure was recorded for 35 minutes. The results obtained showed significant antihypertensive activity both in acute evaluations and in prolonged treatment. Furthermore, data obtained suggests the involvement of nitric oxide release and the opening of calcium-dependent potassium channels. The second study evaluated the ability of gold nanoparticles stabilized in the extract of Pfaffia paniculata (AuNPs-PP), popularly known as Brazilian ginseng, to promote antihypertensive effect and ensure reproductive safety in female SHR rats. The animals were mated and the presence of sperm in the vaginal lavage indicated the first day of pregnancy. Animals were then randomly assigned to receive oral treatment, for 18 days, with AuNPs-PP (0.03, 0.1 and 0.3 mg/kg), anlodipine (5 mg/kg) and vehicle (filtered water; 100 µl per 100 g body weight). Possible signs of toxicity were monitored throughout the experimental period. At the end of the experimental period and before euthanasia, the animals underwent urine collection, electrocardiogram, direct measurement of blood pressure, removal of the mesenteric vascular bed and blood collection for biochemical analysis. After euthanasia, the gravid uterus and ovaries were removed to assess different reproductive parameters. Heart was also removed for morphometric and histopathological analysis. Treatment with AuNPs-PP did not exert diuretic or antihypertensive activity, nor did it impact the results of the electrocardiogram and the reactivity in the mesenteric vascular bed. Serum biochemical parameters and cardiac histopathology were not altered by any of the treatments. No significant changes were also observed in the different reproductive indices and parameters, demonstrating the absence of gestational toxicity. The data obtained allows us to conclude that treatment with AuNPs-PP does not induce cardioprotective effects or reproductive toxicity in pregnant SHR rats.