Papel da liraglutida sobre a função quimiorreflexa e estresse oxidativo de ratas hipertensas ovariectomizadas

Abstract

Methodology: SHR females at 8 weeks of age were OVX or SHAM operated and treated for 30 days s.c. with liraglutide 0.6mg/kg twice daily (OVX Lira; Sham Lira) or saline (OVX Sal; Sham Sal). The femoral artery and vein were catheterized under anesthesia to evaluate the chemoreflex (MAP (ΔmmHg), HR (Δbpm), fR (cpm)); and obtain baseline cardiorespiratory parameters: SBP, MAP, DBP (mmHg), HR (bpm), fR (cpm), VT (tidal volume, mL/Kg-1) and VE (minute ventilation, mL.Kg-1.min-1), in addition to HR and SBP variability in the time domain. The animals were euthanized and the heart and brainstem were used to determination advanced oxidation protein products (AOPP) (μmol/mg of protein), lipid peroxidation (μmol/mg of protein), nitrite/nitrate levels (nmol/mg of protein) and expression of NADPH oxidase (NOX2) and catalase (CAT) proteins (protein/GAPDH) by Western Blot (WB). Data was analyzed by Twoway ANOVA and expressed as mean ± error standard of the mean and level of significance set as p<0.05. The project was approved by CEUA-UFES nº11/2019. Results: The OVX Lira showed greater chemoreflex bradycardia (OVX Sal= - 102±14; OVX Lira= -177±7; n=11), greater heart rate variability (RMSSD: Sham Sal=4.3±0.3, n= 10; OVX Lira=6.6±0.8; n=11), higher expression of CAT in cardiac tissue (OVX Sal=0.4±0.02; OVX Lira=0.7±0.09; n=5) and brainstem (Sham Lira=0.4±0.01; OVX Lira=0.5±0.04; n=5), as well as lower AOPP in cardiac tissue (OVX Sal=0.039±0.002; OVX Lira=0.032±0.001; n=5) and brainstem (OVX Sal=23±0.7; OVX Lira=18±0.8; n=5). Furthermore, OVX increased the expression of NOX2 (OVX Sal=1.96±0.3; Sham Sal=0.95±0.2; n=5) and lipid peroxidation (OVX Sal=0.0013; Sham Sal= 0.0009; n=5) while Lira was able to prevent these changes (OVX Lira: NOX2=1.25±0.3, n=5; MDA=0.0012, n=5) in the heart. Finally, OVX reduced levels of NOx and NO3 - (NOx=10.3±0.3; NO3 - =7.1±0.1) in the brainstem, but lira increased the bioavailability of these metabolites NO (NOx =12.4±0.6; NO3- =8.7±0.5). Conclusion: These results indicate that liraglutide can protect cardiac function through peripheral and central mechanisms associated with improving redox balance in situations of hypertension, ovarian hormone deficiency and nondiabetic conditions. However, more studies are needed to better understand the biological benefits and unravel the mechanism of this important protective effect.