Avaliação do potencial diurético, anti-hipertensivo e cardioprotetor da planta medicinal Gomphrena celosioides Mart. (Amaranthaceae) em ratos

Abstract

Introduction: Gomphrena celosioides Mart., Amaranthaceae, known as "perpétua", is a medicinal plant native to many parts of the world and has several popular uses, including the treatment of kidney stones and urinary tract disorders. Although G. celosioides is used as a diuretic agent, no study had been conducted to evaluate this ethnopharmacological statement. A possible diuretic effect raises questions about its usefulness as an antihypertensive. Objectives of the study: To evaluate the diuretic, antihypertensive and, ultimately, cardioprotective potential of the ethanolic extract of G. celosioides (EEGC) and to elucidate its mechanisms of action. Material and methods: EEGC (30, 100 and 300 mg/kg) was orally administered in rats and urinary volume (UV) and sodium (UNa) were measured for the following 8 h with the aid of metabolic cages. In order to evaluate the role of the nitric oxide (NO), prostaglandin and bradykinin pathway in this effect, it was evaluated whether the lowest effective dose (EEGC 100 mg/kg) maintained diuretic activity in the presence of inhibitors of each of these pathways. Diuretic activity was also measured daily in a 7-day model, after which blood was collected for analysis of angiotensin converting enzyme (ACE) activity, aldosterone and vasopressin. Then the hypotensive effect of EEGC in an acute and in a prolonged model was assessed using hypertensive rats that had undergone Goldblatt surgery. The mean arterial blood pressure (MAP) of the 1K1C (1 kidney, 1 clip) animals was directly measured, by cannulation of the carotid artery, before and after the acute intraduodenal administration of 30, 100 or 300 mg/kg EEGC. For the 4 week trial, 2K1C (2 kidneys, 1 clip) animals received daily oral treatments with EEGC 100 mg/kg or controls (vehicle and enalapril 15 mg/kg) for 28 days. MAP (by tail cuff and at the end by cannulation of the carotid artery) and diuresis were evaluated weekly. Their mesenteric beds were isolated and cannulated to evaluate their pressure variation after addition of vasoactive drugs. Internal organs were weighed and processed for histology and the thickness of the left cardiac ventricle wall was measured. Blood samples were taken for quantification of ACE activity, aldosterone, thiobarbituric acid reactive substances (TBARS) and nitrite. Results: EEGC significantly increased UV and UNa after 8 h comparing to the control group. It was observed that this effect is dependent on the NO, prostaglandin and bradykinin pathways since their inhibitors reduced the diuretic effects of EEGC. In addition, in the prolonged model, this activity was maintained for 7 days and there was a decrease in serum aldosterone. EEGC was able to acutely reduce the MAP of hypertensive animals. In the 4-week test, the EEGC also served as a diuretic and as an antihypertensive, with its MAP at the end of the experiment being close to pre-surgical values. In addition, EEGC reduced the impairment to vascular reactivity induced by renovascular hypertension, since its mesenteric beds, similarly to the group of non-operated animals, presented lower contractility and greater dilatability comparing to the hypertensive control. In addition, the extract promoted inhibition of ACE activity, which also led to lower levels of aldosterone. In the EEGC group, nitrite was increased and TBARS assay showed decreased malondialdehyde. Finally, cardioprotection was observed as the EEGC group showed thinner ventricular walls. Conclusion: EEGC showed acute and prolonged diuretic, natriuretic and antihypertensive effects. These effects were sufficient to promote cardioprotection, and ACE inhibition was proposed as the main mechanism of action. Therefore, these results may have clinical relevance and allow the development of new natural medicines from G. celosioides.