Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?

Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important

Coexpression of rat P2X2 and P2X6 subunits in Xenopus oocytes.

Transcripts for P2X(2) and P2X(6) subunits are present in rat CNS and frequently colocalize in the same brainstem nuclei. When rat P2X(2) (rP2X(2)) and rat P2X(6) (rP2X(6)) receptors were expressed individually in Xenopus oocytes and studied under voltage-clamp conditions, only homomeric rP2X(2) receptors were fully functional and gave rise to large inward currents (2-3 microA) to extracellular ATP. Coexpression of rP2X(2) and rP2X(6) subunits in Xenopus oocytes resulted in a heteromeric rP2X(2/6) receptor, which showed a significantly different phenotype from the wild-type rP2X(2) receptor. Differences included reduction in agonist potencies and, in some cases (e.g., Ap(4)A), significant loss of agonist activity. ATP-evoked inward currents were biphasic at the heteromeric rP2X(2/6) receptor, particularly when Zn(2+) ions were present or extracellular pH was lowered. The pH range was narrower for H(+) enhancement of ATP responses at the heteromeric rP2X(2/6) receptor. Also, H(+) ions inhibited ATP responses at low pH levels (<pH 6.3). The pH-dependent blocking activity of suramin was changed at this heteromeric receptor, although the potentiating effect of Zn(2+) on ATP responses was unchanged. Thus, the rP2X(2/6) receptor is a functionally modified P2X(2)-like receptor with a distinct pattern of pH modulation of ATP activation and suramin blockade. Although homomeric P2X(6) receptors function poorly, the P2X(6) subunit can contribute to functional heteromeric P2X channels and may influence the phenotype of native P2X receptors in those cells in which it is expressed

Studies of Mass and Size Effects in Three-Dimensional Vibrofluidized Granular Mixtures

We examine the steady state properties of binary systems of driven inelastic hard spheres. The spheres, which move under the influence of gravity, are contained in a vertical cylinder with a vibrating base. We computed the trajectories of the spheres using an event-driven molecular dynamics algorithm. In the first part of the study, we chose simulation parameters that match those of experiments performed by Wildman and Parker. Various properties computed from the simulation including the density profile, granular temperature and circulation pattern are in good qualitative agreement with the experiments. We then studied the effect of varying the mass ratio and the size ratio independently while holding the other parameters constant. The mass and size ratio are shown to affect the distribution of the energy. The changes in the energy distributions affect the packing fraction and temperature of each component. The temperature of the heavier component has a non-linear dependence on the mass of the lighter component, while the temperature of the lighter component is approximately proportional to its mass. The temperature of both components is inversely dependent on the size of the smaller component.Comment: 14 Pages, 12 Figures, RevTeX

The catalyzed liquefaction and gasification of coal.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1973.Vita.Bibliography: leaves 385-389.Sc.D

Segregation by thermal diffusion of an intruder in a moderately dense granular fluid

A solution of the inelastic Enskog equation that goes beyond the weak dissipation limit and applies for moderate densities is used to determine the thermal diffusion factor of an intruder immersed in a dense granular gas under gravity. This factor provides a segregation criterion that shows the transition between the Brazil-nut effect (BNE) and the reverse Brazil-nut effect (RBNE) by varying the parameters of the system (masses, sizes, density and coefficients of restitution). The form of the phase-diagrams for the BNE/RBNE transition depends sensitively on the value of gravity relative to the thermal gradient, so that it is possible to switch between both states for given values of the parameters of the system. Two specific limits are considered with detail: (i) absence of gravity, and (ii) homogeneous temperature. In the latter case, after some approximations, our results are consistent with previous theoretical results derived from the Enskog equation. Our results also indicate that the influence of dissipation on thermal diffusion is more important in the absence of gravity than in the opposite limit. The present analysis extends previous theoretical results derived in the dilute limit case [V. Garz\'o, Europhys. Lett. {\bf 75}, 521 (2006)] and is consistent with the findings of some recent experimental results.Comment: 10 figure

Thermalization of an anisotropic granular particle

We investigate the dynamics of a needle in a two-dimensional bath composed of thermalized point particles. Collisions between the needle and points are inelastic and characterized by a normal restitution coefficient $\alpha<1$. By using the Enskog-Boltzmann equation, we obtain analytical expressions for the translational and rotational granular temperatures of the needle and show that these are, in general, different from the bath temperature. The translational temperature always exceeds the rotational one, though the difference decreases with increasing moment of inertia. The predictions of the theory are in very good agreement with numerical simulations of the model.Comment: 7 pages, 6 Figures, submitted to PRE. Revised version (Fig1, Fig5 and Fig6 corrected + minor typos

An integrated study of earth resources in the State of California based on ERTS-1 and supporting aircraft data

There are no author-identified significant results in this report