O efeito anti-hipertensivo do ácido sinápico está associado à melhora da sensibilidade do barorreflexo e da disfunção autonômica em ratos espontaneamente hipertensos: ensaios pré-clínicos e in sílico

Abstract

Sinapic acid is one of the four hydroxynamic acids most commonly found in nature; present in fruits, vegetables, oilseeds, cereal grains. It has several pharmacological activities such as antioxidant, anti-inflammatory, anxiolytic and anti-hypertensive, the latter in L-NAME rats. However, there are no reports of its effects in the hypertension model with spontaneously hypertensive rats (SHR) as well as no data on its participation in the autonomic modulation of blood pressure and its control mechanisms. The present study aimed to evaluate the effects induced by sinapic acid on cardiovascular parameters of normotensive (WKY) and spontaneously hypertensive (SHR) rats. For this, a combination of in vivo protocols performed in WKY and SHR rats. Thus, the effects of oral treatment for 14 days with sinapic acid on blood pressure, heart rate, autonomic sympathetic and parasympathetic activity, and baroreflex sensitivity were evaluated. Oral treatment with sinapic acid was able to reduce blood pressure only in SHR rats (184.5 ± 6,114 vs. 148.3 ± 5.39 mmHg, p < 0.05), without causing changes in the heart rate of the animals. Autonomic function was assessed using pharmacological tools; and synapic acid increased parasympathetic activity (ΔFC: +39 ± 5.2 vs. +129 ± 6 bpm, p ˂ 0.05) and decreased sympathetic hyperactivity in SHR rats (ΔPAM: -64.83 ± 4.5 vs - - 40.8 ± 7.7 mmHg; p ˂ 0.05). Regarding the pharmacologically induced baroreflex with vasoactive drugs, oral treatment with sinapic acid was able to improve the sensitivity of the baroreflex (- 1.192 ± 0.1441 vs. -2.366 ± 0.1885 bpm / mmHg, p < 0.05 ) by increasing the parasympathetic gain index (-0.683 ± 0.111 versus -2.814 ± 0.430 bpm / mmHg, p < 0.05), with no smaller difference in relation to the sympathetic one. Sinapic acid treatment was also able to reduce serum oxidative stress in SHR rats (54.75 ± 6.2 vs. 18.1 ± 1.3 nmol / ml, p ˂ 0.05). Finally, in in silico assays, sinapic acid has good theoretical bioavailability after oral administration, good solubility, stability and absorption, as well as low oral toxicity, as well as possible other pharmacological activities on the cardiovascular system. These data obtained an antihypertensive effect of sinapic acid, and this effect is associated with the improvement of the baroreflex and the autonomic dysfunction present in these animals. The reduction of oxidative stress is involved, at least in part, in the effects caused by the compound. The characteristics of sinapic acid suggested by the study on silico may be involved in the properties of the compound, encouraging research on sinapic acid as an alternative for the treatment of systemic arterial hypertension.