Ciências Fisiológicas
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- ItemCaracterização da atividade biológica de um peptídeo inibidor da ECA derivado do Kefir na hipertensão dependente de angiotensina em camundongos(Universidade Federal do Espírito Santo, 2021-08-20) Aires, Rafaela; Meyrelles, Silvana dos Santos; https://orcid.org/0000-0003-0167-4093; http://lattes.cnpq.br/7731215198101947; https://orcid.org/0000-0002-9532-9401; http://lattes.cnpq.br/5449202639864996; Baldo, Marcelo Perim; https://orcid.org/0000-0002-7673-3580; http://lattes.cnpq.br/7820422119282248; Nogueira, Breno Valentim; https://orcid.org/0000000221990635; http://lattes.cnpq.br/0011229320439147; Santos, Leonardo dos; https://orcid.org/0000-0002-4340-6364; http://lattes.cnpq.br/4132087001362623; Gouvêa, Sônia Alves; https://orcid.org/000000015180471X; http://lattes.cnpq.br/7268228122543743The benefits of Kefir consumption are due, in part, to the rich composition of bioactive molecules released from fermentation. However, the bioactive components and mechanisms of action involved in the antihypertensive effect of this probiotic still need to be explored. A previous study sequenced 35 angiotensin-converting enzyme (ACE) inhibitory peptides in Kefir. Here, the in vivo actions of the Kef-1 peptide, an ACE inhibitor derived from Kefir, was evaluate in an angiotensin II-dependent hypertension model. Firstly, Kef-1 inhibitory activity on ACE was evaluate in vitro. In mice with 2-kidney, 1-clip (2K1C) hypertension, the short (3 days) and long-term (7 days) hemodynamic effects were evaluated after oral administration of Kef-1. For in vivo protocols, C57Bl/6 male mice were submitted to clipping of the left renal artery to produce 2K1C hypertension. The short (3 days) and long-term (7 days) hemodynamic effects were evaluated after oral administration of Kef-1. Furthermore, after 7 days of treatment, systemic and local (vascular smooth muscle cells, SMC) oxidative stress and inflammation were analyzed. Kef-1 was able to inhibit at 59.6% the in vitro activity ACE in comparation to captopril. After 3 hours, Kef-1 reduced (p<0.05) systolic BP (SBP), diastolic BP (DBP) and media BP (MBP) when compared with vehicle treatments (-25.8±3.9, -26.0±3.8, -26.4±4.3 mmHg, respectively). SBP, DBP and MBP also were reduced (p<0.05) after 7 days of Kef-1 treatment (-22.2±3.9; -31.6±2.6; MBP: -24.3±3.2 mmHg, respectively). Kef1 reduced (p<0,05) HR in both short (~13%) and long-treatment (~7%). At 7 days following Kef-1, ROS production, lipidic peroxidation and DNA damage was lower in blood cells (p<0.05) when compared to the 2K1C group (~10%, ~23%, ~54%, respectively). In SMC, Kef-1 was able to reduce (p<0.05) ROS production (~22%) and cellular apoptosis (~58%) in comparation to the 2K1C group. Kef-1 contributed to attenuate NADPHox and mitochondrial participation in SMC. Furthermore, Kef-1 reduced SMC apoptosis (59%, p<0.05). The antiinflammatory effect of Kef-1 was evidenced in the reduction (p<0.05) of the systemic levels of pro-inflammatory cytokines (TNFα: ~34%, IFNγ: ~22%, MCP1: ~33%, IL-6:~16%) and the activity of myeloperoxidase (~57%). In SMC, Kef-1 reduced by 75% (p<0.05) the intracellular levels of NO. The aorta of hypertensive 20 mice treated with Kef-1 showed lower thickness of wall (~28%, p<0.05) and partial restoration of endothelial structure. In conclusion, this study revealed the anti-hypertensive potential of the Kef-1 heptapeptide through its antioxidant and anti-inflammatory properties in an experimental model of Ang II-dependent hypertension. These new findings help to clarify the mechanisms involved in the benefits of Kefir beverage in the hypertension.
- ItemCurso temporal das alterações na variabilidade da frequência cardíaca e da pressão arterial após infarto do miocárdio em ratos(Universidade Federal do Espírito Santo, 2015-06-29) Aires, Rafaela; Dantas, Eduardo Miranda; Mill, José Geraldo; Baldo, Marcelo PerimIntroduction: Myocardial infarction (MI) acutely impairs the cardiac pump and reduces the cardiac output (CO). Blood pressure (BP) control depends on continuous adjustments of the autonomic balance directed to the heart and blood vessels. Such adjustments change after MI and may vary over time Objective: To determine the time course of the autonomic balance adjustments in the acute (1-3 days), sub-acute (7 days) and chronic (21 days) phases of MI in rats. Methods: The autonomic balance was assessed by temporal and spectral analysis of the blood pressure (BPV) and heart rate (HRV) variability. Pulsatile BP recordings (30 min) were obtained in the awake and unrestrained animals with MI or sham operated (SO). Data are means ± SE. Results: Heart rate remained unchanged in the SO group over time and it was higher (P<0.01) in MI rats at 1 and 3 days after MI (SO-1= 356±9.7 vs MI-1= 438±13 bpm; SO3= 346±17; MI-3= 411±8.4 bpm) with tendency to recover normal values thereafteer (SO-7= 345±4.2 vs MI-7= 382±14 bpm; SO-21= 339±10 vs MI-21= 375±17 bpm) (P<0.001 for the interaction F-test, two-way ANOVA). MI was followed by an overall reduction of HRV in both HF and LF bands of the spectral analysis. The power of HF (n.u.) was significantly lower in MI-1 (P <0.01) and MI-3 days rats (P <0.05) compared with their time-control groups (SO-1= 68±4 vs MI-1= 35.3±4.3; SO-3= 71±5.8 vs MI-3= 45.2±3.8) without difference thereafter (SO-7= 69.2±4.8 vs MI-7= 56±5.8; SO-21= 73±4 vs MI-21= 66±6.6), (P=0.001 for the interaction F-test, two-way ANOVA). Along the observation period, MI rats also showed reduced BPV, mostly dependent on significant reduction of the LF band in absolute and normalized units (SO-1= 39.3±7 vs MI1= 13±3.5; SO-3= 55±4.5 vs MI-3= 35±4.7; SO-7= 46.8±4.5 vs MI-7= 25±2.8; SO-21= 45.7±5 vs MI-21= 21.4±2.8; P=0.001 for the interaction F-test; two-way ANOVA). The HF component of BPV was unaffected after MI Conclusion: Our data suggest that the initial tachycardia in the acute phase MI seems to be mainly due to removal of the parasympathetic modulation on heart beats. Recovery of basal heart rate values is timely associated to the recovery of the HF component of HRV