Name: BRUNELLA FARO KLIPPEL

Publication date: 25/08/2016
Advisor:

Namesort descending Role
ELISARDO CORRAL VASQUEZ Advisor *

Examining board:

Namesort descending Role
DALTON VALENTIM VASSALLO Internal Examiner *
ELISARDO CORRAL VASQUEZ Advisor *
MARCELLA PORTO TAVARES External Examiner *

Summary: Studies have shown that the probiotic Kefir has beneficial effects on the treatment of hypertension. The aim of this study was to evaluate the effect of chronic treatment with Kefir on cardiac autonomic tone and arterial baroreflex in spontaneously hypertensive rats (SHR). Methods: Male Wistar and SHR rats at 4 months of age, were separated into 3 groups Wistar, SHR and SHR-Kefir treated for 60 days with Kefir (0,3ml/100g) by gavage. The animals were anesthetized and catheters were implanted in the femoral artery and vein for drugs injection and pulsatile arterial blood pressure (PAP), mean arterial pressure (MAP) and heart rate (HR) records, respectively. The relative contribution of parasympathetic and sympathetic cardiac autonomic tone, were estimated in conscious animals via bolus injections of N-methyl-atropine (2 mg/kg) and atenolol (2mg/kg), respectively. The intrinsic heart rate (IHR) was estimated after double blockade with the drugs cited above. The baroreflex sensitivity was tested in concious animals through increases or decreases in blood pressure (25 mmHg) by bolus injections of phenylephrine (5 mg/kg) and sodium nitroprusside (40 mg/kg) under atropine and atenolol blockade 24 and 48 h later. The analysis of blood pressure (BPV) and heart rate variability (HRV) was performed through spectral analysis, autoregressive method in the time domain (variance of systolic pressure and RR intervals) and frequency domain (very low, low and high-frequency, VLF, LF, HF, respectively). At the end of experiment, the heart and kidneys were removed and weighed to hypertrophy analysis. Results: As expected the SHR group had higher levels of SBP, DBP, MAP and HR (204±8, 144±4, 167±4 mmHg and 355±9 bpm, p<0.05, respectively) compared to Wistar rats (140±8, 88±2 and 104±2 mmHg 328±12 bpm, respectively). Kefir treatment significantly attenuated these parameters (169±8, 116±6, 134±6 mmHg and 324±12 bpm, respectively). SHR group showed left ventricular hypertrophy (22±1.4 mg/mm, p<0.05) when compared with Wistar rats (17.1±1.4 mg/mm, p<0.05). And treatment with Kefir reduced this hypertrophy when normalized by tibia length (19±1.2 mg/mm, p<0.05) in SHR. The vagal tone in Wistar group was +120 bpm and +40 bpm in SHR group. Kefir partially recovered vagal tone (+90 bpm) in treated SHR. The sympathetic tone in Wistar group was bpm -30 and -90 bpm in SHR group. In Kefir treated SHR rats sympathetic tone was reduced to -25 bpm. The baroreflex sensitivity was significantly decreased in SHR group (bradycardic reflex ~50%) as well as the relative contribution of vagal and cardiac sympathetic
components when compared to the Wistar group. In the SHR rats treated with Kefir both bradycardic reflex (~40%, p<0.05) and the gain (-35%,) were significatively improved. Atropine blockade abolished the bradycardic reflex and baroreflex gain equally in the 3 groups. The SHR group showed a decrease in tachycardic reflex (38%, p<0.05) and gain deacrese (32%, p<0.05) when compared with Wistar group. In Kefir treated rats these responses were improved (~8% and ~12%, p<0.05, respectively). Atenolol blockade reduced reflex tachycardic in SHR when compared with Wistar and SHR treated with Kefir the normalized (7±2.8, 14±2.4 and 12±2.4 bpm), similar effects were observed in gain (0.26±0.10, 0.53±0.11 and 0.46±0.12 bpm/mmHg, respectively). HRV and HR-LF were higher in SHR (730±150 ms2 and 82±10 ms2) when compared with Wistar (247±46 ms2 and 39±9 ms2) and SHR rats treated with Kefir (478±80 ms2 and 56±10 ms2). There were no differences when comparing the FC-HF results among the three groups. Both VBP and BP-LF showed a significant increase in SHR group (73±9 mmHg2, 13±2 mmHg2) when compared to Wistar rats (22±3 mmHg2 and 3.7±0.4 mmHg2). Kefir treatment reduced these values (65±8 mmHg2 and 8±2 mmHg2). Finally, analysis of spontaneous baroreflex showed a sensitivity decrease in the SHR group (1.36±0.09 ms2/mmHg) compared with Wistar group (1.75±0.11 ms2/mmHg). Kefir treatment did not improve this sensitivity (1.48±0.09 ms2/mmHg). Conclusion: After 60 days with Kefir treatment, SHR animals showed decreased SBP, DBP and MAP, besides a reduction of cardiac hypertrophy. In addition, Kefir treatment partially reversed the loss of vagal tone, the sympathetic tone increase and baroreflex dysfunction of hypertensive animals.

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