Ação do nerolidol puro e complexado em lipossoma sobre o sistema cardiovascular em modelo animal de hipertensão arterial

Abstract

Systemic arterial hypertension (SAH) is one of the main risk factors for the development of cardiovascular diseases (CVDs), which have a high morbidity and mortality rate worldwide. Studies point out that the use of natural products reflects positively on the treatment of SAH, among which are terpenes, whose therapeutic properties have an effect on the cardiovascular system. Nerolidol (NRD) is a sesquiterpene that has anti-inflammatory, antioxidant and cardioprotective action. However, due to its low solubility and high volatility, it is necessary to include it in a formulation that increases oral bioavailability and absorption. The aim of this study was to evaluate the cardiovascular effects of pure and liposome-complexed NRD (NLIP) in an animal model of hypertension. Male Wistar rats (CEPA: 7471310521/3941310521) hypertensive (L-NAME, 20 mg/kg/day, 7 days) were used. Measurements of mean arterial pressure (MAP) and heart rate (HR) were performed before and after intravenous (i.v.) administration of NRD (1; 5; 10; 20 mg/kg) and after oral administration (200 mg/kg; gavage ) of the NRD or NLIP. After oral treatment, the hemodynamic effects were evaluated for 48h. In intravenous treatment, NRD produced a hypotensive response at all doses (-19.8 ± 3.87, -25.5 ± 3.08, -36.10 ± 4.87, and –45.53 ± 4.61, n = 7) and bradycardia at doses of 10 mg/kg and 20 mg/kg (-32.55 ± 11.97 and –54.11 ± 8.18, n = 7). Hypotension was inhibited by pretreatments (10 mg/kg and 20 mg/kg) with atropine (ATR) (-3.54 ± 1.71, -9.31 ± 6.14, n=5)., L -NAME (- 12.72 ± 6.38, and –14.86 ± 5.16, n = 7), and indomethacin (INDO) (-19.36 ± 4.56 and -20.43 ± 6.11 , n = 6), whereas bradycardia was attenuated with ATR (-0.83 ± 0.30 and –1.57 ± 1.51, n=6)., L-NAME (-10.96 ± 9.67 , and –9.33 ± 9.48, n=6) and hexamethonium (HEXA) (-1.40 ± 2.40 and –6.26 ± 2.03, n=5). In the oral treatment, NRD and NLIP induced antihypertensive responses, with the highest responses found within 48 hours (112 ± 5.04% mmHg) of NLIP; 0.5h and 1h (137 ± 4.47% and 139 ± 4.47% mmHg, respectively) of NRD. The results demonstrate that NRD induces hypotension with bradycardia intravenously and, when administered orally in its pure and complexed form, showed a promising antihypertensive effect.