High‐fat sucrose (HFS) diet in aged individuals causes severe weight gain (obesity) with much higher risk of cardiovascular diseases such as hypertension or atherosclerosis. Endothelial dysfunction is a major contributor for these vascular disorders. We hypothesize that prolonged ingestion of HFS diet by aged mice would accentuate endothelial dysfunction in the small resistance arteries. Male C57BL/6J mice at 12 weeks of age were divided into four groups and fed either normal chow (NC) or high‐fat sucrose diet (HFS). Young group received NC for 4 months, and high‐fat diet (HFD) for 3 months and 1 month HFS + 10% Sucrose (HFS diet). Aged mice received NC for 12 months. Aged HFS group received HFD for 4 months + 1 month HFD + 10% sucrose + 8 months HFD. Total body weight, plasma blood glucose levels, and glucose tolerance were determined in all groups. Isolated mesenteric arteries were assessed for arterial remodeling, myogenic tone, and vasomotor responses using pressure and wire myography. Both young and aged HFS mice showed impaired glucose tolerance (Y‐NC, 137 ± 8.5 vs. Y‐NC HFS, 228 ± 11.71; A‐NC, 148 ± 6.42 vs. A‐HFS, 225 ± 10.99), as well as hypercholesterolemia (Y‐NC 99.50 ± 6.35 vs. Y‐HFS 220.40 ± 16.34 mg/dL; A‐NC 108.6 ± vs. A‐HFS 279 ± 21.64) and significant weight gain (Y‐NC 32.13 ± 0.8 g vs. Y‐HFS 47.87 ± 2.18 g; A‐NC 33.72 vs. A‐HFS 56.28 ± 3.47 g) compared to both groups of mice on NC. The mesenteric artery from mice with prolonged HFS diet resulted in outward hypertrophic remodeling, increased stiffness, reduced myogenic tone, impaired vasodilation, increased contractility and blunted nitric oxide (NO) and EDH‐mediated relaxations. Ebselen, a peroxinitrite scavenger rescued the endothelium derived relaxing factor (EDHF)‐mediated relaxations. Our findings suggest that prolonged diet‐induced obesity of aged mice can worsen small resistance artery endothelial dysfunction due to decrease in NO and EDHF‐mediated relaxation, but, EDHF‐mediated relaxation is a major contributor to overall endothelial dysfunction.
We report a direct Monte Carlo simulation of an energy-dependent t&molecular reaction system of the type A+ B in which the rates of the reactions of specific states Ai of A increase with their internal energies. Intermolecular exchange of translational and internal energies among colliding species Ai+A,~A,+A, is incorporated with use of a simple flexible statistical model satisfying all requirements of momentum and energy conservation, microscopic reversibility, and equilibrium. The required calculations are straight forward and rapid. The observed variation of overall reaction rate with pressure deviates from that of a simple Lindemann-Christiansen mechanism. For unrestricted energy exchange allowing transitions between all levels of A the deviations are small. For restricted (ladder) energy exchange limited to transitions up or down one level per collision the deviations are larger and the behavior is similar to that observed in a number of experimental studies.
We report direct Monte Carlo simulations of a chemical reaction system with bimolecular and termolecular dissociation and recombination reactions of the type M ϩAB M ϩAϩB. The simulations are carried out at the molecular level using a simple flexible reaction model for termolecular reactions satisfying all the requirements of momentum and energy conservation, microscopic reversibility, and equilibrium. Energy transfer among reactants and products is included. The method is especially useful for treating reaction systems with nonequilibrium distributions and coupled gas dynamic-reaction effects. For systems with thermally equilibrated reactants the observed behavior is identical to that predicted by conventional methods.
Obesity has been linked to the development of cardiovascular diseases 1 and is a multifaceted metabolic syndrome correlated with hyperglycemia, insulin resistance, adipose tissue inflammation, endothelial dysfunction, peripheral vascular resistance, and hypertension. [2][3][4] Obesity is also implicated in the development of arterial stiffness due to increased consumption of western diet. 5 Although stiffness increases with aging, obesity accelerates the stiffening process at a much younger age, especially in females. 5,6 There are several contributory factors for the development of obesity associated increase in arterial stiffness such as changes in the intimal, medial, and adventitial layers of the artery 6 and due to endothelial dysfunction. 7 Furthermore, increased oxidative stress in obesity could also increase arterial stiffness. 8 Increased production of reactive oxygen species (ROS) due to activation of xanthine oxidase in the vasculature in obesity has been implicated in the development of arterial stiffness. 6 In addition, obesity is also associated with
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