Bisphenol A contamination in infant rats: molecular, structural, and physiological cardiovascular changes and the protective role of kefir.

The effects of bisphenol A (BPA) contamination on the cardiovascular function still are not clear. Here, we evaluated the vascular effects of BPA and the protective actions of kefir in infant rats. Animals (25 days old) were treated with BPA (100 µg/Kg/day) for 60 days (BPA group), or administered kefir (0.3 mL/100 g) in addition to BPA (BPA kefir group), compared with non-treated rats (Control group).The vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine and specific blockers. The balance between reactive oxygen species (ROS) and nitric oxide (NO) was assessed through flow cytometry in the vascular tissue. The BPA group developed high blood pressure (+10%) and the analysis of vascular reactivity showed an impaired ACh-induced relaxation (~80%). The further analysis by using NADPH, NOS and COX blockers revealed that the impaired vasorelaxation was due to increased ROS production (+12%), NO bioavailability (-12%) and increased vasoconstriction to prostanoids (+36%) compared with the Control group. Kefir treatment reverted those effects significantly. Analysis of the aortic cells showed increased •O2- production (1942±39 a.u.) and decreased NO bioavailability (1250±30 a.u.) compared with the Control group (1374±146 and 2777±25 a.u., P<.05) and kefir reverted these values (1298±57 and 2517±57 a.u.). Contamination by BPA in this model caused hypertension and endothelial dysfunction and it was accompanied by a vascular ROS/NO imbalance, damage of endothelial layer and pro-apoptotic effects. The novelty is that the treatment using probiotic kefir was able to attenuate the progression the above BPA effects.

Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats.

AIMS: It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. METHODS: SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of ß1-adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. RESULTS: Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively. Spectral analysis also showed an impairment of spontaneous BRS in SHR, but kefir-treatment caused only a tendency to reverse this result. CONCLUSIONS: The novelty of this study is that daily chronic consumption of a low dose of kefir reduced the impairment of the cardiac autonomic control of HR and of the impaired BRS in SHR.

Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

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.