Name: BRENNA LEPAUS MONTEIRO VIEIRA
Publication date: 29/09/2017
Advisor:
Name |
Role |
|---|---|
| ELISARDO CORRAL VASQUEZ | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| AGATA LAGES GAVA | Internal Examiner * |
| BIANCA PRANDI CAMPAGNARO | Co advisor * |
| ELISARDO CORRAL VASQUEZ | Advisor * |
| THIAGO DE MELO COSTA PEREIRA | External Examiner * |
Summary: Among the characteristics of renovascular hypertension we can highlight oxidative stress and endothelial dysfunction. Objective: To evaluate the effects of kefir on the endothelial dysfunction of rats with renovascular hypertension. Method: Wistar rats were divided into 3 groups Sham, 2K1C and 2K1C-Kefir treated for 60 days with Kefir (0.3ml/100g), by oral gavage. The arterial pressure was monitored during treatment through tail plethysmography and at the end of treatment the animals were submitted to direct PA recording. The aorta was used in the construction of dose-response curves to Acetylcholine (ACh), sodium nitroprusside (NPS), and Phenylephrine (Phe). Kidneys were removed and used for angiotensin I, II and 1-7 analysis and ACE (angiotensin converting enzyme) activity. Aortas were used for oxidative stress analysis using flow cytometry. Values indicate the mean ± SEM. * P <0.05 compared to the Sham group; # P <0.05 relative to the 2K1C group. RESULTS: The 2K1C group had higher SBP, DBP, MAP (203 ± 11, 129 ± 4, 179 ± 6 mmHg) than the sham group (139 ± 11, 67 ± 5, 94 ± 2). In the Kefir-treated rats the PAS, PAD and PAM decreased significantly when compared to the 2R1C group (180 ± 11, 89 ± 7, 128 ± 4 mmHg). The animals in the 2K1C group presented endothelial dysfunction, which was observed in the relaxation curve endothelium-dependent (Rmax: 56 ± 4% *) when compared to controls (Rmax: 85 ± 4%), and kefir treatment was able to reverse this dysfunction (Rmax: 72 ± 5% #). Vascular smooth muscle dysfunction was also observed in the NPS curve in the 2K1C group (Rmax: 87 ± 3% *) compared to the sham group (Rmax: 96 ± 2%), and kefir treatment failed to restore this dysfunction (Rmax: 90 ± 3%). The 2K1C group showed increased the response to phenylephrine (Rmax: 80 ± 2% *) when compared to sham group (Rmax: 73 ± 2%), and kefir treatment also did not decrease these responses in treated hypertensive animals (Rmax: 86 ± 3%). The role of NO and Prostanoids was verified by blocking with L-NAME and Indomethacin and we observed that relaxation to ACh in 2R1C animals was decreased (dAUC: NO: 162 ± 9 *; Prostanoids Prostanoids: 86 ± 6 * au ) As compared to controls (dAUC: NO: 255 ± 11 *, Prostanoids: 29 ± 0.2 * au) and
restored in kefir-treated animals (NO: 247 ± 8 #; Prostanoids: 54 ± 2% au). We also observed that ERO'S participation in the dysfunction of hypertensive animals (dAUC: dAUC: 92 ± 11 *), when compared with normotensive animals (dAUC: 1.2 ± 0.02), and similarly, kefir reestablished ERO levels in the treated animals (dAUC: 40 ± 6%). In the analysis of oxidative stress in the aorta and blood performed by flow cytometry, we observed that 2K1C animals showed an increase in the production of ROS in the blood (O-2: 1771 ± 32, H2O2: 562 ± 41 a.u) and in the aorta (O-2: 551 ± 42, H2O2: 929 ± 86 a.u) when compared to the sham group ( O-2: 251 ± 5, H2O2: 516 ± 60 a.u blood) (O-2: 1129 ± 85, H2O2: 191 ± 2 a.u aorta) and kefir treatment was able to decrease the production of these species in the blood ( O-2: 260 ± 60, H2O2: 370 ± 64 a.u) and in the aorta O-2: 1080 ± 70, H2O2: 198 ± 11 a.u). ACE activity was higher in serum (174 ± 11 nmol/min/ mg) and in the non-clipped kidney (0.48 ± 0.04 nmol/min/mg) of 2K1C rats when compared to the sham group (151 ± 6 nmol/min/mg serum and 0.35 ± 0.03 nmol/min/mg non-clipped kidney). Treatment with kefir decreased enzyme activity (148 ± 8 nmon/min/mg serum, 0.31 ± 0.01 nmol/min/mg non-clipped kidney). Therefore, we conclude that 60 days kefir treatment in rats with renovascular hypertension has several beneficial effects, attenuating hypertension, improving endothelial dysfunction and oxidative stress, as well as decreasing ACE activity.
