Reactive oxygen species and cyclooxygenase 2-derived thromboxane A2 reduce angiotensin II type 2 receptor vasorelaxation in diabetic rat resistance arteries

Angiotensin II has a key role in the control of resistance artery tone and local blood flow. Angiotensin II possesses 2 main receptors. Although angiotensin II type 1 receptor is well known and is involved in the vasoconstrictor and growth properties of angiotensin II, the role of the angiotensin II type 2 receptor (AT2R) remains much less understood. Although AT2R stimulation induces vasodilatation in normotensive rats, it induces vasoconstriction in pathological conditions involving oxidative stress and cyclooxygenase 2 expression. Thus, we studied the influence of cyclooxygenase 2 on AT2R-dependent tone in diabetes mellitus. Mesenteric resistance arteries were isolated from Zucker diabetic fatty (ZDF) and lean Zucker rats and studied using in vitro using wire myography. In ZDF rats, AT2R-induced dilation was lower than in lean rats (11% versus 21% dilation). Dilation in ZDF rats returned to the control (lean rats) level after acute superoxide reduction (Tempol and apocynin), cyclooxygenase 2 inhibition (NS398), or thromboxane A(2) synthesis inhibition (furegrelate). Cyclooxygenase 2 expression and superoxide production were significantly increased in ZDF rat arteries compared with arteries of lean rats. After chronic treatment with Tempol, AT2R-dependent dilation was equivalent in ZDF and lean rats. Chronic treatment of ZDF rats with NS398 also restored AT2R-dependent dilation to the control (lean rats) level. Plasma thromboxane B(2) (thromboxane A(2) metabolite), initially high in ZDF rats, was decreased by chronic Tempol and by chronic NS398 to the level found in lean Zucker rats. Thus, in type 2 diabetic rats, superoxide and thromboxane A(2) reduced AT2R-induced dilation. These findings are important to take into consideration when choosing vasoactive drugs for diabetic patients

Average stresses and force fluctuations in non-cohesive granular materials

A lattice model is presented for investigating the fluctuations in static granular materials under gravitationally induced stress. The model is similar in spirit to the scalar q-model of Coppersmith et al., but ensures balance of all components of forces and torques at each site. The geometric randomness in real granular materials is modeled by choosing random variables at each site, consistent with the assumption of cohesionless grains. Configurations of the model can be generated rapidly, allowing the statistical study of relatively large systems. For a 2D system with rough walls, the model generates configurations consistent with continuum theories for the average stresses (unlike the q-model) without requiring the assumption of a constitutive relation. For a 2D system with periodic boundary conditions, the model generates single-grain force distributions similar to those obtained from the q-model with a singular distribution of q's.Comment: 18 pages, 10 figures. Uses aps,epsfig,graphicx,floats,revte

Internal states of model isotropic granular packings. III. Elastic properties

In this third and final paper of a series, elastic properties of numerically simulated isotropic packings of spherical beads assembled by different procedures and subjected to a varying confining pressure P are investigated. In addition P, which determines the stiffness of contacts by Hertz's law, elastic moduli are chiefly sensitive to the coordination number, the possible values of which are not necessarily correlated with the density. Comparisons of numerical and experimental results for glass beads in the 10kPa-10MPa range reveal similar differences between dry samples compacted by vibrations and lubricated packings. The greater stiffness of the latter, in spite of their lower density, can hence be attributed to a larger coordination number. Voigt and Reuss bounds bracket bulk modulus B accurately, but simple estimation schemes fail for shear modulus G, especially in poorly coordinated configurations under low P. Tenuous, fragile networks respond differently to changes in load direction, as compared to load intensity. The shear modulus, in poorly coordinated packings, tends to vary proportionally to the degree of force indeterminacy per unit volume. The elastic range extends to small strain intervals, in agreement with experimental observations. The origins of nonelastic response are discussed. We conclude that elastic moduli provide access to mechanically important information about coordination numbers, which escape direct measurement techniques, and indicate further perspectives.Comment: Published in Physical Review E 25 page

Influence of hyperhomocysteinemia on the cellular redox state - Impact on homocysteine-induced endothelial dysfunction

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteines deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteineinduced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide

Invasion impact is conditioned by initial vegetation states

Abstract Biological invasion is a crucial problem in the world because of its negative consequences for protected areas. The degradation stage of vegetation might affect the success of invasion. One of the most abundant and threatening invasive species is the common milkweed (Asclepias syriaca L.) which has invaded already 23 countries of Europe and in several habitat types its further spreading is promoted by climate change. Pannonian sand grassland is one of the most threatened habitat by common milkweed invasion. Therefore, invasion in sand grassland vegetation is an important issue. However, the effects of the invasive plant in the open sand grassland are rather controversial. In order to clarify the existing contradictory results, the study was carried out in a strictly protected area, near Fülöpháza (Hungary) in a reserve core area in a UNESCO biosphere reserve. Microcoenological study was applied to determinate the fine-scale community characteristics of non-invaded and invaded stands in natural and seminatural vegetation and data were processed by Juhász-Nagy's information theory models. Shannon diversity of species combinations (compositional diversity) which describes the ways of the coexistence of species, and the number of realized species combinations were used for measuring beta diversity. Differences between stands were analyzed by two-way ANOVA. The maximum compositional diversity of species and main life-forms (annuals, perennials and cryptogams) did not differ significantly between the non-invaded and invaded stands. In contrast, significantly larger characteristic areas of compositional diversity were detected in the invaded stands. Based on these results, it could be concluded that diversity of species combinations did not change but those values have shifted to coarser scales in case of invaded stands. The direction of this change suggests a kind of impoverishment in the presence of Asclepias. Thus, it is worth mentioning from the invasion management point of view that protection of the habitats against disturbance is a more cost-effective and successful way than protection against the establishment or extirpation of invasive species, since disturbance facilitates the invasions throughout the impoverishment of the community

Internal states of model isotropic granular packings. I. Assembling process, geometry and contact networks

This is the first paper of a series of three, reporting on numerical simulation studies of geometric and mechanical properties of static assemblies of spherical beads under an isotropic pressure. Frictionless systems assemble in the unique random close packing (RCP) state in the low pressure limit if the compression process is fast enough, slower processes inducing traces of crystallization, and exhibit specific properties directly related to isostaticity of the force-carrying structure. The different structures of frictional packings assembled by various methods cannot be classified by the sole density. While lubricated systems approach RCP densities and coordination number z^*~=6 on the backbone in the rigid limit, an idealized "vibration" procedure results in equally dense configurations with z^*~=4.5. Near neighbor correlations on various scales are computed and compared to available laboratory data, although z^* values remain experimentally inaccessible. Low coordination packings have many rattlers (more than 10% of the grains carry no force), which should be accounted for on studying position correlations, and a small proportion of harmless "floppy modes" associated with divalent grains. Frictional packings, however slowly assembled under low pressure, retain a finite level of force indeterminacy, except in the limit of infinite friction.Comment: 29 pages. Published in Physical Review

Pore-scale Modeling of Viscous Flow and Induced Forces in Dense Sphere Packings

We propose a method for effectively upscaling incompressible viscous flow in large random polydispersed sphere packings: the emphasis of this method is on the determination of the forces applied on the solid particles by the fluid. Pore bodies and their connections are defined locally through a regular Delaunay triangulation of the packings. Viscous flow equations are upscaled at the pore level, and approximated with a finite volume numerical scheme. We compare numerical simulations of the proposed method to detailed finite element (FEM) simulations of the Stokes equations for assemblies of 8 to 200 spheres. A good agreement is found both in terms of forces exerted on the solid particles and effective permeability coefficients