Name: THATIANY JARDIM BATISTA
Publication date: 16/10/2023
Examining board:
Name |
Role |
|---|---|
| NAZARE SOUZA BISSOLI | Advisor |
Summary: Aim: investigate the effect of Liraglutide treatment on the chemoreflex and
cardiac oxidative stress of ovariectomized (OVX) spontaneously hypertensive
(SHR) rats.
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 (mmHg), HR
(bpm), 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) (mol/mg of
protein), lipid peroxidation (mol/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.
