Search

Your search keyword '"Barron Brady"' showing total 2 results
Start Over Author "Barron Brady" Topic allopurinol
2 results on '"Barron Brady"'

1. Xanthine oxidase inhibition protects against Western diet-induced aortic stiffness and impaired vasorelaxation in female mice.

Author

Lastra G, Manrique C, Jia G, Aroor AR, Hayden MR, Barron BJ, Niles B, Padilla J, and Sowers JR

Subjects
Animals, Aorta drug effects, Enzyme Inhibitors administration & dosage, Female, Mice, Mice, Inbred C57BL, Oxidative Stress drug effects, Oxidative Stress physiology, Vascular Stiffness drug effects, Vasodilation drug effects, Vasomotor System drug effects, Vasomotor System physiology, Xanthine Oxidase antagonists & inhibitors, Allopurinol administration & dosage, Aorta physiology, Diet, Western, Uric Acid blood, Vascular Stiffness physiology, Vasodilation physiology, Xanthine Oxidase metabolism
Abstract

Consumption of a high-fat, high-fructose diet [Western diet (WD)] promotes vascular stiffness, a critical factor in the development of cardiovascular disease (CVD). Obese and diabetic women exhibit greater arterial stiffness than men, which contributes to the increased incidence of CVD in these women. Furthermore, high-fructose diets result in elevated plasma concentrations of uric acid via xanthine oxidase (XO) activation, and uric acid elevation is also associated with increased vascular stiffness. However, the mechanisms by which increased xanthine oxidase activity and uric acid contribute to vascular stiffness in obese females remain to be fully uncovered. Accordingly, we examined the impact of XO inhibition on endothelial function and vascular stiffness in female C57BL/6J mice fed a WD or regular chow for 16 wk. WD feeding resulted in increased arterial stiffness, measured by atomic force microscopy in aortic explants (16.19 ± 1.72 vs. 5.21 ± 0.54 kPa, P < 0.05), as well as abnormal aortic endothelium-dependent and -independent vasorelaxation. XO inhibition with allopurinol (widely utilized in the clinical setting) substantially improved vascular relaxation and attenuated stiffness (16.9 ± 0.50 vs. 3.44 ± 0.50 kPa, P < 0.05) while simultaneously lowering serum uric acid levels (0.55 ± 0.98 vs. 0.21 ± 0.04 mg/dL, P < 0.05). In addition, allopurinol improved WD-induced markers of fibrosis and oxidative stress in aortic tissue, as analyzed by immunohistochemistry and transmission electronic microscopy. Collectively, these results demonstrate that XO inhibition protects against WD-induced vascular oxidative stress, fibrosis, impaired vasorelaxation, and aortic stiffness in females. Furthermore, excessive oxidative stress resulting from XO activation appears to play a key role in mediating vascular dysfunction induced by chronic exposure to WD consumption in females.

Published
2017
Full Text
View/download PDF

2. Uric acid promotes vascular stiffness, maladaptive inflammatory responses and proteinuria in western diet fed mice

Author

Javad Habibi, Annayya R. Aroor, Dongqing Chen, Gerald A. Meininger, Francisco I. Ramirez-Perez, Vincent G. DeMarco, Guanghong Jia, James R. Sowers, Zhe Sun, Camila Manrique, Ravi Nistala, Luis A. Martinez-Lemus, Adam Whaley-Connell, and Barron Brady

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Xanthine Oxidase, Vascular smooth muscle, Endocrinology, Diabetes and Metabolism, Allopurinol, 030204 cardiovascular system & hematology, medicine.disease_cause, Article, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Endocrinology, Vascular Stiffness, Internal medicine, medicine, Animals, Xanthine oxidase, Inflammation, Kidney, Proteinuria, medicine.disease, Uric Acid, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, chemistry, Diet, Western, Arterial stiffness, Uric acid, medicine.symptom, Oxidative stress, medicine.drug
Abstract

Objective Aortic vascular stiffness has been implicated in the development of cardiovascular disease (CVD) and chronic kidney disease (CKD) in obese individuals. However, the mechanism promoting these adverse effects are unclear. In this context, promotion of obesity through consumption of a western diet (WD) high in fat and fructose leads to excess circulating uric acid. There is accumulating data implicating elevated uric acid in the promotion of CVD and CKD. Accordingly, we hypothesized that xanthine oxidase(XO) inhibition with allopurinol would prevent a rise in vascular stiffness and proteinuria in a translationally relevant model of WD-induced obesity. Materials/Methods Four-week-old C57BL6/J male mice were fed a WD with excess fat (46%) and fructose (17.5%) with or without allopurinol (125 mg/L in drinking water) for 16 weeks. Aortic endothelial and extracellular matrix/vascular smooth muscle stiffness was evaluated by atomic force microscopy. Aortic XO activity, 3-nitrotyrosine (3-NT) and aortic endothelial sodium channel (EnNaC) expression were evaluated along with aortic expression of inflammatory markers. In the kidney, expression of toll like receptor 4 (TLR4) and fibronectin were assessed along with evaluation of proteinuria. Results XO inhibition significantly attenuated WD-induced increases in plasma uric acid, vascular XO activity and oxidative stress, in concert with reductions in proteinuria. Further, XO inhibition prevented WD-induced increases in aortic EnNaC expression and associated endothelial and subendothelial stiffness. XO inhibition also reduced vascular pro-inflammatory and maladaptive immune responses induced by consumption of a WD. XO inhibition also decreased WD-induced increases in renal TLR4 and fibronectin that associated proteinuria. Conclusions Consumption of a WD leads to elevations in plasma uric acid, increased vascular XO activity, oxidative stress, vascular stiffness, and proteinuria all of which are attenuated with allopurinol administration.

Published
2017

Catalog

Books, media, physical & digital resources
See catalog results