Investigação etnofarmacológica dos efeitos cardiovasculares e renais da Blutaparon portulacoides (A. Hil.) Mears em ratos espontaneamente hipertensos

Abstract

Systemic arterial hypertension (SAH) is a chronic, multifactorial and non-communicable disease, in which there is a persistent elevation of systolic and/or diastolic pressure ≥ 140 and/or 90 mmHg. Blutaparon portulacoides (A.St.-Hil.) Mears is a Brazilian plant species that is widely used in folk medicine. The present study investigated the cardiovascular and renal effects of aqueous extract of B. portulacoides (AEBP) against hypertension in spontaneously hypertensive rats (SHR). First, the herbaceous was collected for the preparation of the aqueous extract, for this, the whole plant (roots, stems and leaves) was used. In sequence, the chemical composition was analyzed by mass spectrometry in ultra performance liquid chromatography (ESI-MS). Then, acute toxicity was evaluated for 14 days in 10 female Wistar rats at 90 days of age. Then, after proving the safety of AEBP, prolonged diuresis was performed in 180-day-old rats, with 50 male SHR rats divided into 5 experimental groups (n=10) and 10 male Wistar-Kyoto rats (naive group), the animals were treated once a day for 28 days with different doses of AEBP extract (30, 100 and 300 mg/kg), hydrochlorothiazide (HCTZ; 25 mg/kg) and filtered water (negative control and naive: 10 ml/kg). The diuretic activity was evaluated on days 1, 14 and 28. In addition, the role of prostaglandins and cyclic nitric oxide potassium guanosine monophosphate (NO-cGMP-K+) in diuretic activity was also investigated, using 30 male SHR rats divided into 5 experimental groups (n=6) and 6 male Wistar-Kyoto rats (naive group), the animals received doses of indomethacin (5 mg/kg), L-nitro-arginine-methyl-ester (60 mg/kg), methylene blue (100 mg/kg), tetraethylammonium (10 mg/kg) and filtered water (NC and naive: 5 ml/kg), and after 1 hour they were treated with AEBP (300 mg/kg), HCTZ (25 mg/kg), and filtered water (CN and naive 0.2 ml/100 g). At the end of the treatments, the animals were submitted to the evaluation of electrocardiographic activity, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MAP) and heart rate (HR) by the direct method. Then, the mesenteric vascular bed (MVL) and the left kidney were isolated and prepared for perfusion to assess vascular reactivity to different concentrations of vasoactive substances (phenylephrine, angiotensin II, acetylcholine and sodium nitroprusside). In addition, blood samples were collected for serum biochemical analyses, as well as tissue samples from the aorta, heart and contralateral kidney, obtained to investigate the tissue antioxidant system, relative weight, cardiac morphometry and histology of the aforementioned tissues. Phytochemical analysis identified the presence of caffeic acid, ferulic acid and several flavonoids in the AEBP. As previously mentioned, the extract did not show toxicity or any sign of behavioral change was observed in Wistar rats. Finally, prolonged treatment with AEBP (300 mg/kg) induced significant diuretic activity in male rats by activating the NO-cGMP-K+ channel pathway. These effects reduced blood pressure and oxidative stress and prevented hypertension-induced renal vascular dysfunction and left ventricular hypertrophy.