Wild Blueberry-Rich Diets Affect the Contractile Machinery of the Vascular Smooth Muscle in the Sprague-Dawley Rat

Dorothy J. Klimis-Zacas,Anastasia Z. Kalea,Patrick D. Harris,Cynthia Norton 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.1

Weanling male Sprague–Dawley rats were randomly fed a control diet (AIN-93) (C) or a blueberry diet (B) for 13 weeks, or a reverse diet (R) (C diet for 13 weeks, switched to the B diet for 8 weeks). Aortas were excised, and two intact and two endothelium-denuded rings were immersed in tissue baths containing physiological salt solution at 37°C and aerated with 95% O2 and 5% CO2 (pH 7.4). Following equilibration and preconditioning under 1.5-g preload, cumulative dose–response curves were generated with six doses of the 1-adrenergic receptor-selective agonist L-phenylephrine (L-Phe, 108–3 106 M) and relaxed with one dose of acetylcholine (3 106 M) to assess intact endothelium. The maximum force of contraction (Fmax) and vessel sensitivity (pD2) were determined in intact and endothelium-denuded rings. A two-way analysis of variance test revealed that blueberry-fed animals (B and R diets) developed a significantly lower Fmax (0.873 0.0463 and 0.9266 0.0463 g, respectively) when contracted with L-Phe, compared with the animals on the C diet (1.109 0.0463 g) (P .05). The pD2 of the intact rings was not significantly different among diet groups. Additionally, diet did not significantly affect the mean Fmax or pD2 of endothelium-denuded rings. Our results indicate for the first time that wild blueberries incorporated into the diet affect the vascular smooth muscle contractile machinery by suppressing the 1-adrenergic receptor agonist-mediated contraction while having no effect on membrane sensitivity of the endothelial or vascular smooth muscle cell layer. Furthermore, their mechanism of action seems to be accomplished through an endothelium-dependent pathway.

The Effects of Wild Blueberry Consumption on Plasma Markers and Gene Expression Related to Glucose Metabolism in the Obese Zucker Rat

Stefano Vendrame,Alice Zhao,Thomas Merrow,Dorothy Klimis-Zacas 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.6

Impaired fasting blood glucose is one of the landmark signs of metabolic syndrome, together with hyperinsulinemia, dyslipidemia, hypertension, and a chronic proinflammatory, pro-oxidative, and prothrombotic environment. This study investigates the effect of wild blueberry (WB) consumption on blood glucose levels and other parameters involved in glucose metabolism in the obese Zucker rat (OZR), an experimental model of metabolic syndrome. Sixteen OZRs and 16 lean littermate controls (lean Zucker rat [LZR]) were fed an 8% enriched WB diet or a control (C) diet for 8 weeks. Plasma concentrations of glucose, insulin, glycated hemoglobin GHbA1c, resistin, and retinol-binding protein 4 (RBP4) were measured. Expression of the resistin, RBP4, and glucose transporter GLUT4 genes was also determined both in the liver and the abdominal adipose tissue (AAT). Plasma glycated hemoglobin HbA1c, RBP4, and resistin concentrations were significantly lower in OZRs following the WB diet ( - 20%, - 22%, and - 27%, respectively, compared to C diet, P < .05). Following WB consumption, resistin expression was significantly downregulated in the liver of both OZRs and LZRs ( - 28% and - 61%, respectively, P < .05), while RBP4 expression was significantly downregulated in the AAT of both OZRs and LZRs ( - 87% and - 43%, respectively, P < .05). All other markers were not significantly affected following WB consumption. In conclusion, WB consumption normalizes some markers related to glucose metabolism in the OZR model of metabolic syndrome, but has no effect on fasting blood glucose or insulin concentrations.

Angiogenesis is Differentially Modulated by Anthocyanin and Phenolic Acid Extracts from Wild Blueberry (V. angustifolium) Through PI3K Pathway

Panagiotis Tsakiroglou,James Weber,Sharon Ashworth,Cristian Del Bo,Dorothy Klimis-Zacas 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.3

Wild blueberries rank very high in anthocyanins (ACNs) and phenolic acids (PA) among other berries. Previous work from our group has documented their beneficial effects. In this study, human umbilical vein endothelial cells were used, and ACNs, PAs, and their combination (ACNs:PAs) at concentrations of 0.002, 8, 15, 60, and 120 μg/mL were tested for endothelial tube formation. Treatment with ACNs decreased, while treatment with PAs and ACNs:PAs increased overall endothelial cell tube formation compared to control. Endothelial cells exposed to ACNs downregulated gene expression of AKT1 and endothelial nitric oxide synthase (eNOS), while PAs upregulated AKT1 and vascular endothelial growth factor (VEGF) gene expression. Combination of ACNs:PAs decreased gene expression of AKT1 and eNOS, while protein levels of AKT1 increased. In summary, based on the type of wild blueberry extract, angiogenesis is differentially modulated and is concentration dependent. Further experiments will delineate the mechanism(s) of the differential action of the aforementioned extracts on angiogenesis.

Vascular Reactivity Is Affected by Dietary Consumption of Wild Blueberries in the Sprague-Dawley Rat

Kalea, Anastasia Z.,Clark, Kateryna,Schuschke, Dale A.,Klimis-Zacas, Dorothy J. The Korean Society of Food Science and Nutrition 2009 Journal of medicinal food Vol.12 No.1

We have previously reported that consumption of blueberry-enriched (BB) diets attenuates the arterial contractile response to ${\alpha}_1$-adrenergic stimuli and affects vasomotor tone via endothelium-related pathways. The present study wa designed to evaluate vascular function and responsiveness in aortas of weanling male Sprague-Dawley rats fed a control (C) or a BB diet for 7 weeks. Vascular ring studies were conducted in 3-mm isolated rat aortic ring preparations to investigate vasoconstriction induced by L-phenylephrine (Phe) ($10^{-8}-3\;{\times}\;10^{-6}\;M$) and vasorelaxation induced by acetylcholine (ACh($10^{-8}-3\;{\times}\;10^{-6}\;M$). Agonists were used alone and in the presence of nitric oxide (NO) synthase and cyclooxygenase (COX) inhibitors. We observed a significantly diminished vasoconstrictor response to Phe in aortic rings from rats fed the BB diet. Inhibition of NO synthase but not COX caused a significant increase in the constrictor response in both dietary groups, with the BB group having the greater response. Similarly, the participation of the NO pathway in endothelium-dependent vasorelaxation induced by ACh was greater in the rats fed a BB diet, while COX inhibition showed no effect on maximum ACh-induced vasorelaxation in any diet group. The vessel sensitivity of BB aortic rings to the vasoconstrictor and vasodilator was significantly reduced when compared to controls. We have concluded that diets enriched with blueberries, fed for 7 weeks in Sprague-Dawley rats, seem to affect NO metabolic pathways in the aorta at basal and stimulated levels.

Whole Red Raspberry (Rubus idaeus)-Enriched Diet Is Hepatoprotective in the Obese Zucker Rat, a Model of the Metabolic Syndrome

Natalie E. VandenAkker,Stefano Vendrame,Panagiotis Tsakiroglou,Marissa McGilvrey,Dorothy Klimis-Zacas 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.8

Non-alcoholic fatty liver disease is a major risk factor of the metabolic syndrome (MetS). The effect of whole red raspberry (WRR) consumption on lipid metabolism was investigated in the obese Zucker rat (OZR), a model for the MetS. Male OZRs (n = 16) and their lean littermates (lean Zucker rat) (n = 16) at 8 weeks of age were placed on a control or an 8% WRR-enriched diet for 8 weeks. Plasma triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels, and hepatic concentration of TG were measured. The expression of nine genes related to lipid metabolism was evaluated, both in liver and adipose tissue. A WRR-enriched diet reduced plasma cholesterol and HDL-C and increased plasma TG, while it decreased hepatic TG accumulation in the OZR. The OZR assigned to a WRR exhibited upregulation of microsomal triglyceride transfer protein (Mttp) and downregulation of fatty acid synthase (Fas) expression in the liver. Results showed a decrease in accumulation of liver TG and gene expression modulation of enzymes and transcription factors associated with lipid metabolism, suggesting a possible hepatoprotective role of a WRR-enriched diet.

Vascular Reactivity Is Affected by Dietary Consumption of Wild Blueberries in the Sprague-Dawley Rat

Anastasia Z. Kalea,Kateryna Clark,Dale A. Schuschke,Dorothy J. Klimis-Zacas 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.1

We have previously reported that consumption of blueberry-enriched (BB) diets attenuates the arterial contractile response to α1-adrenergic stimuli and affects vasomotor tone via endothelium-related pathways. The present study was designed to evaluate vascular function and responsiveness in aortas of weanling male Sprague-Dawley rats fed a control (C) or a BB diet for 7 weeks. Vascular ring studies were conducted in 3-mm isolated rat aortic ring preparations to investigate vasoconstriction induced by L-phenylephrine (Phe) (10−8–3 × 10−6 M) and vasorelaxation induced by acetylcholine (ACh) (10−8–3 × 10−6 M). Agonists were used alone and in the presence of nitric oxide (NO) synthase and cyclooxygenase (COX) inhibitors. We observed a significantly diminished vasoconstrictor response to Phe in aortic rings from rats fed the BB diet. Inhibition of NO synthase but not COX caused a significant increase in the constrictor response in both dietary groups, with the BB group having the greater response. Similarly, the participation of the NO pathway in endothelium-dependent vasorelaxation induced by ACh was greater in the rats fed a BB diet, while COX inhibition showed no effect on maximum ACh-induced vasorelaxation in any diet group. The vessel sensitivity of BB aortic rings to the vasoconstrictor and vasodilator was significantly reduced when compared to controls. We have concluded that diets enriched with blueberries, fed for 7 weeks in Sprague-Dawley rats, seem to affect NO metabolic pathways in the aorta at basal and stimulated levels.