Efeito cardioprotetor de Aloysia polystachya (Griseb) Moldenke em um modelo de múltiplos fatores de risco cardiovascular em ratos

Abstract

Cardiovascular diseases (CVD) are the leading causes of death among chronic noncommunicable diseases worldwide. There are risk factors that lead to an increase in the occurrence and/or aggravation of CVD, these include unhealthy nutrition, physical inactivity, dyslipidemia, hyperglycemia, obesity, hypertension, among others. Experimental models are widely disseminated in preclinical research, for the identification of new pharmacological potentials related to the cardiovascular system, mainly using rodents. Among these studies, those originating from reports of popular and traditional use of medicinal plants stand out. Aloysia polystachya (Griseb) Moldenke, popularly known as “burrito”, is used to treat different disorders of the cardiovascular system. Therefore, the general objective of the present work was to validate a preclinical model of multiple cardiovascular risk factors in rats (Step 1) and to evaluate the cardioprotective effect of the essential oil from A. polystachya (Step 2). For step 1, a model of multiple cardiovascular risk factors that associates hypertension, hypothyroidism and dyslipidemia was developed. Two models of hypertension were used: renovascular hypertension (2 kidneys – 1 clip (2K1C)) and spontaneously hypertensive rats (SHR). The naïve group was composed of normotensive rats. Twelve weeks after surgery to induce renovascular hypertension, rats in the 2K1C and SHR groups underwent thyroidectomy. The high-fat diet was then implemented for 6 weeks. Renal function, biochemical markers, electrocardiographic profile, blood pressure, vascular reactivity of the mesenteric bed, histopathology and morphometry were investigated in samples from the heart, kidney, liver, subclavian and carotid arteries. Both experimental models induced dyslipidemia, impaired renal function and hepatic steatosis, accompanied by increase in levels of different serum inflammatory markers and oxidative stress. These changes promoted target organ damage in all hypertensive rats. The data support a viable alternative model that involves multiple cardiovascular risk factors and resembles evidenced conditions in human, especially in the case of SHR, which exhibited more severe pathophysiological changes. For step 2, essential oil from A. polystachya leaves (EOAP) was extracted. The acute toxicity of EOAP in 10 female Wistar rats, equally divided into two groups, control (n = 5) and 2000 mg/kg (n = 5). In the pharmacological assay, animals were randomized and divided into six groups: five groups of SHR animals (n = 8) and one group of normotensive animals (naïve; n = 8). SHR animals underwent thyroidectomy to induce hypothyroidism. Hypertensive animals were divided into groups: EOAP dose 1 (1.47 mg/kg); EOAP dose 2 (4.40 mg/kg); EOAP dose 3 (13.20 mg/kg); negative control (vehicle) and positive control (rosuvastatin; 5 mg/kg) all treated orally once daily for six weeks. Concomitantly with the treatment, a high-fat diet was implemented for all groups, except for the naïve (standard diet). After 6 weeks, renal function, biochemical markers, electrocardiographic profile, blood pressure, vascular reactivity of the mesenteric bed, histopathology and morphometry of organ samples were investigated. The results obtained suggest that EOAP did not promote signs of toxicity and prevented renal, electrocardiographic and hemodynamic alterations, maintaining systolic pressure levels similar to those found in naïve animals. It can be concluded that the experimental model that associates hypertension, dyslipidemia and hypothyroidism presents itself as an efficient alternative to mimic pathophysiological, biochemical and histopathological changes present in a context of multiple cardiovascular risk factors. Furthermore, it was possible to demonstrate the cardioprotective effect of EOAP in a model of multiple cardiovascular risk factors.