Determinação do efeito de cepas de Limosilactobacillus fermentum sobre a pressão arterial e função autonômica na prole de ratos oriundos de mães dislipidêmicas

Abstract

Maternal dyslipidemia contributes to the development of arterial hypertension (AH) associated with sympathetic hyperactivity, impaired baroreflex control, augmented peripheral chemoreceptor sensitivity and unbalance in the gut microbiota composition in adulthood. Studies indicate that the administration of probiotics can be effective in the improvement of disorders in lipid metabolism, attenuating oxidative stress and reducing blood pressure (BP). Thus, the general objective of this study was to investigate the effects of the intervention with a probiotic formulation of L. fermentum on cardiovascular and metabolic parameters in rats offspring exposed to maternal dyslipidemia. The protocols were approved by CEUA / UFPB (nº 9492260418/2018). Pregnant Wistar rats (n = 14) were fed a control diet (CTL = 7) or a dyslipidemic diet (DLP = 7) during pregnancy and lactation. After weaning, the male and female offspring received a commercial diet until the 90 days of age. The rats were divided into three groups: CTL group + saline solution (n = 14; 7 males and 7 females), DLP group + saline solution (n = 14; 7 males and 7 females) and DLP group + probiotic formulation of L. fermentum (n = 14; 7 males and 7 females). The intervention with the probiotic formulation of L. fermentum containing the strains 139, 263 and 296 (109 CFU / mL) was performed daily by gavage from post-weaning to adulthood (30th to 90th day of age). After 8 weeks of treatment, blood was collected for biochemical tests, oral glucose tolerance (OGTT) and insulin tolerance (ITT) tests, fecal samples were collected to microbial viable counts, and finally, rats were anaesthetised with ketamine (80 mg/kg, i.p.) and xylazine (10 mg/kg, i.p.) to insert polyethylene catheters in the femoral artery and vein for later measurement of baseline BP and heart rate (HR), spectral analysis of systolic blood pressure and pulse interval and sympathetic-vagal balance. Then, 0.04% KCN (100 µl/rat, i.v.) was used to evaluate the sensitivity of peripheral chemoreceptors. To evaluate baroreflex control, sodium nitroprusside (25 µg/kg) and phenylephrine (8 µg/kg) were administered. The contribution of sympathetic tone to BP maintenance was evaluated by administration of hexamethonium (25 mg/kg, i.v). The intervention with probiotic formulation of L. fermentum in DLP male and female offspring attenuated the serum levels of total cholesterol (TC) (p <0.05) and malondialdehyde (MDA) (p <0.05) and exhibited higher serum levels of high-density lipoprotein (HDL) (p <0.05), but did not attenuate insulin resistance (IR) (p> 0.05) induced by maternal dyslipidemia. In addition, the DLP groups of both sexes that received the probiotic formulation of L. fermentum also showed improvement in fecal Lactobacillus sp. counts (p<0.05), pressor response (p<0.05) and sympathetic tone (p<0.05) when compared to the non-treated DLP groups. These results indicate that the probiotic formulation of L. fermentum may effectively attenuate the sympathoexcitatory response induced by the peripheral chemoreflex, as well as reduce the sympathetic tone and oxidative stress, being a promising strategy to prevent hypercholesterolemia and, consequently, the development of AH in adult offspring.