title: Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.
abstract: BACKGROUND
  The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue.
  
  
  RESULTS
  Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the recruitment of endothelial progenitor cells was decreased in the non-treated SHR and partially restored by kefir treatment.
  
  
  CONCLUSIONS
  Kefir treatment for 60 days was able to improve the endothelial function in SHR by partially restoring the ROS/NO imbalance and the endothelial architecture due to endothelial progenitor cells recruitment.
authors.affiliation: Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. andreiafriques@hotmail.com.
authors.forename: Andreia G F
authors.initials: AG
authors.lastname: Friques
authors.affiliation: Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. clarisse.arpini@uvv.br.
authors.forename: Clarisse M
authors.initials: CM
authors.lastname: Arpini
authors.affiliation: Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. ieda@uvv.br.
authors.forename: Ieda C
authors.initials: IC
authors.lastname: Kalil
authors.affiliation: Division of Nephrology, McMaster University, Hamilton, ON, Canada. agatagava@hotmail.com.
authors.forename: Agata L
authors.initials: AL
authors.lastname: Gava
authors.affiliation: Laboratory of Translational Physiology, Federal University of Espirito Santo, Vitoria, ES, Brazil. marcos.emescam@gmail.com.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Leal
authors.affiliation: Laboratory of Translational Physiology, Federal University of Espirito Santo, Vitoria, ES, Brazil. cella.porto@gmail.com.|Institute of Education, Science and Technology (IFES), Vila Velha, ES, Brazil. cella.porto@gmail.com.
authors.forename: Marcella L
authors.initials: ML
authors.lastname: Porto
authors.affiliation: Department of Morphology, Federal University of Espirito Santo, Vitoria, ES, Brazil. brenovalentim@gmail.com.
authors.forename: Breno V
authors.initials: BV
authors.lastname: Nogueira
authors.affiliation: Laboratory of Translational Physiology, Federal University of Espirito Santo, Vitoria, ES, Brazil. anandatd@yahoo.com.br.
authors.forename: Ananda T
authors.initials: AT
authors.lastname: Dias
authors.affiliation: Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. tadeu.uggere@uvv.br.
authors.forename: Tadeu U
authors.initials: TU
authors.lastname: Andrade
authors.affiliation: Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. pereiratmc@gmail.com.|Institute of Education, Science and Technology (IFES), Vila Velha, ES, Brazil. pereiratmc@gmail.com.
authors.forename: Thiago Melo C
authors.initials: TM
authors.lastname: Pereira
authors.affiliation: Laboratory of Translational Physiology, Federal University of Espirito Santo, Vitoria, ES, Brazil. meyrelle.vix@terra.com.br.
authors.forename: Silvana S
authors.initials: SS
authors.lastname: Meyrelles
authors.affiliation: Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. biancacampagnaro@yahoo.com.br.
authors.forename: Bianca P
authors.initials: BP
authors.lastname: Campagnaro
authors.affiliation: Pharmaceutical Sciences Graduate Program, Vila Velha University, Vila Velha, ES, Brazil. evasquez@terra.com.br.|Laboratory of Translational Physiology, Federal University of Espirito Santo, Vitoria, ES, Brazil. evasquez@terra.com.br.
authors.forename: Elisardo C
authors.initials: EC
authors.lastname: Vasquez
mesh_terms: D000818:Animals; D043302:Cultured Milk Products; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005434:Flow Cytometry; D006973:Hypertension / Q000503:physiopathology*; D008855:Microscopy, Electron, Scanning; D019936:Probiotics; D051381:Rats; D011918:Rats, Inbred SHR