116 research outputs found

    Hematocrit Ratio of Blood Within Mammalian Kidney and Its Significance for Renal Hemodynamics

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    Evidence is presented indicating that the dynamic hematocrit of intra-renal blood is normally about one-half that in blood entering or leaving the kidney. The hematocrit ratio of intrarenal blood, relative to that in arterial blood, varies with the corpuscular concentration in arterial blood and inversely with the renal arterial blood pressure. When the blood pressure is reduced from 140 to 50 mm Hg, the vascular volume of the kidney decreases from 24% to 19% of the kidney volume and the kidney weight decreases by a like amount (i.e. 5%). Owing to the increased intrarenal hematocrit, however, the absolute quantity of red cells in kidneys removed at low pressure is usually greater than in their contralateral controls removed at high pressure. A theory is advanced to take account of the low dynamic hematocrit ratio in intrarenal blood and its variations with arterial pressure and corpuscular concentration. The theory supposes that red cells are progressively separated from plasma by a process of plasma skimming in the interlobular arteries. The deeper glomeruli are supplied primarily with plasma, leaving a highly viscous, cell-rich component of the blood to supply the terminal arterioles. After traversing the efferent arterioles, the cell-rich moiety of the blood is presumed to pass through a short circulation (preferential channels for red cells) bypassing the peritubular capillary network. The energy for the separation process is presumed to be supplied by the kinetic energy of renal arterial blood; the separation process is therefore dependent upon velocity and cell concentration. Applications of the theory to the following topics in renal physiology are discussed: a) the dynamic hematocrit of intrarenal blood; b) autoregulation of the renal circulation as a function of arterial pressure and corpuscular composition; c) afferent and efferent arteriolar resistance and the mechanism of regulation of glomerular filtration rate; d) renal extraction of PAH and Diodrast; e) oxygen supply of the kidney and its variation with blood flow. </jats:p

    Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina:insights into X-linked Retinitis Pigmentosa and associated ciliopathies

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    Mutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR 1-19 and RPGR ORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors

    Altered Permeability of Cell Membranes

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    Renal Extraction of PAH and of Diodrast-I<sup>131</sup> as a Function of Arterial Red Cell Concentration

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    The cell separation theory of renal hemodynamics predicts that the renal extraction of substances secreted by the tubules should vary with the concentration of red cells in arterial blood. This prediction has been tested in anesthetized cats and dogs breathing oxygen. The renal extractions of PAH and of trace concentrations of Diodrast-I131 were found to be smooth and reversible functions of the arterial red cell concentration. The transfer maxima of these substances were unaffected by removal of red cells and the extraction ratios decreased as a function of arterial hematocrit ratio even when the renal plasma flow was maintained constant. The results indicate that at low red cell concentrations about 50% of the renal plasma flow bypasses the tubular elements of the kidney. According to the cell separation theory this extra-tubular flow of plasma takes place through a short circulation which normally contains a cell-rich moiety of the blood. </jats:p

    Role of Red Blood Corpuscles in Regulation of Renal Blood Flow and Glomerular Filtration Rate

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    Renal blood flow was measured as a function of arterial red cell concentration in acute experiments on anesthetized cats breathing oxygen. Renal blood flow changed only slightly when the arterial red cell concentration was varied over the range 20–55%, despite large changes in the viscosity of blood as measured in a glass tube or in a perfused hindleg. When the red cell concentration was progressively reduced below 20%, however, the blood flow (measured at constant pressure) increased greatly, despite the fact that blood viscosity changes very little in this range of cell concentrations. Renal blood flow and glomerular filtration rate (creatinine clearance) were measured as a function of arterial pressure at normal and at very low arterial red cell concentrations. Autoregulation of both renal blood flow and filtration rate was partly or wholly abolished at low red cell concentrations. Autoregulation returned when cells were restored. The experimental results are explicable in terms of the cell-separation theory of renal hemodynamics (1). According to this theory the renal blood flow and glomerular filtration rate are largely controlled by the efficiency of separation of red cells from plasma in the interlobular arteries. Many observations which were previously attributed to differential changes in afferent and efferent arteriolar resistance can be equally well accounted for in terms of the cell-separation theory. </jats:p

    Pathways of cycloleucine transport in killifish small intestine.

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    By using blocking concentrations of competitors, i.e., concentrations of other neutral amino acids that cause maximal inhibition, cycloleucine transport into slices or everted sacs of killifish (fundulus heteroclitus) small intestine could be partitioned into three pathways. One is apparently not mediated, a second is inhibited by all neutral amino acids tested (component 1), and a third, is inhibited by alpha-aminocarboxylic acids (component 2), but not by beta-alanine or taurine. Both mediated pathways were Na dependent, and each yielded a linear double reciprocal plot of initial slice uptake vs. cycloleucine concentration. Apparent Kt and Vmax values for component 1 were 0.03 mM and 33 pmol/mg tissue per 3 min, respectively; corresponding values for component 2 were 0.12 mM and 28 pmol/mg tissue per 3 min. Additional experiments with an intestinal brush border membrane vesicle preparation indicate that these mediated components reflect true differences in carrier specificity rather than the differential effects of inhibitors on metabolism or on the Na gradient that drives cycloleucine transport.</jats:p

    p-Aminohippuric acid transport into brush border vesicles isolated from flounder kidney

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    p-Aminohippuric acid (PAH) transport was investigated in brush border vesicles isolated from renal proximal tubules of the winter flounder. Three characteristics of carrier-mediated transport were demonstrated: 1) unlabeled PAH inhibited the uptake of [3H]PAH; 2)[3H]PAH efflux from the vesicles was stimulated in the presence of unlabeled PAH in the extravesicular medium; and 3) PAH influx was inhibited by 2,4-dinitrophenol (DNP) and 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene (SITS). D-Glucose plus a sodium gradient stimulated PAH uptake, as did a K2SO4 gradient plus valinomycin, suggesting that PAH is transported as an anion. In contrast, PAH uptake into a membrane fraction containing mainly basal-lateral plasma membranes exhibited a larger inhibition by probenecid but a smaller inhibition by unlabeled PAH and SITS. Thus, carrier-mediated transfer of PAH driven by the electrochemical potential difference for PAH is demonstrated in the brush border membrane of the flounder kidney. </jats:p
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