Avaliação dos efeitos cardiovasculares e renais do ácido alfa-lipóico em ratos com hipertensão renovascular no modelo dois-rins-um-clipe (2R1C)

Abstract

Cardiovascular diseases (CVD) are one of the main causes of death in the world, among which systemic arterial hypertension (HAS) stands out. The pathophysiology of hypertension is a risk factor for the development of acute kidney injury, tubular injury, changes in microcirculation and endothelial dysfunction. The aim of this study was to investigate the cardiovascular effects of α-lipoic acid (LA) in normotensive (SHAM) and hypertensive (2R1C) rats, using an in vivo and in vitro approach, seeking to elucidate the possible mechanisms involved in these effects. Wistar rats were used in the two-kidney-one-clip (2R1C) hypertension experimental model and in only 2 groups were treated with AL for 14 days, once a day, at a dose of 0.1 ml / kg via gavage. The animals were divided into 4 groups randomly: SHAM surgery (SHAM) n = 5, hypertensive 2R1C (2R1C) n = 6, SHAM surgery + LIPOIC ACID (SHAM / AL) n = 4 and hypertensive 2R1C + LIPOIC ACID (2R1C / AL) n = 5. The project was approved by the Ethics Committee on the Use of Animals / UFC under protocol number 2867020519. It was the one-way and two-way ANOVA statistical tests, in addition to the Tukey post-test, with p <0.05. After the induction of hypertension and treatment with LA, studies were carried out to analyze the intake of daily water volume and weight of the ration, urinary volume, left kidney / right kidney ratio (Renal Index), organ relationships and body weight, vascular reactivity in aortas isolated from rats against agents such as phenylephrine (PHE), acetylcholine (Ach) and sodium nitroprusside (SNP). In parallel to the pharmacological studies, histological and histomorphometric analyzes of the aorta, heart and kidneys and biochemical analysis using urea and urinary creatinine were performed to study kidney damage. The maximum efficiency curve (Emax) showed a reduction compared to the contraction performed by PHE in 2R1C-AL animals, thus demonstrating that the treatment with AL was able to promote a reduction in the vasoconstriction mechanism observed in these animals. It was observed through biochemical analysis of 24h urine that LA did not alter the levels of urea and creatinine. The histology results showed that the treatment was not significantly statistical in promoting histomorphological changes present over the aortic lumen and in the adventitial / mean ratio. It was concluded that the AL showed a response in the contractile mechanism in animals 2R1C-AL in the study of vascular reactivity, however, a response in the relaxation mechanism was expected in that subject, however, there was no difference in relation to 2R1C. It was found that there were no statistically significant changes in biochemical and histomorphometric analyzes with the treatment caused by the pre-established hypertension induction process.