scholarly journals Injury to the Endothelial Surface Layer Induces Glomerular Hyperfiltration Rats with Early-Stage Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Chunyang Zhang ◽  
Yao Meng ◽  
Qi Liu ◽  
Miao Xuan ◽  
Lanyu Zhang ◽  
...  
Keyword(s):  
Surface Layer ◽  
Particle Density ◽  
Early Stage ◽  
Diabetic Rats ◽  
Mesangial Matrix ◽  
Sprague Dawley ◽  
Endothelial Surface Layer ◽  
Sprague Dawley Rats ◽  
Endothelial Surface

Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidencein vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes.

scholarly journals Microvascular blood viscosity in vivo and the endothelial surface layer

2005 ◽  
Vol 289 (6) ◽  
pp. H2657-H2664 ◽  
Author(s):  
A. R. Pries ◽  
T. W. Secomb
Keyword(s):  
Surface Layer ◽  
Blood Viscosity ◽  
Flow Resistance ◽  
Vessel Diameter ◽  
Viscosity Data ◽  
Endothelial Surface Layer ◽  
Rat Mesentery ◽  
Endothelial Surface

The apparent viscosity of blood in glass tubes declines with decreasing diameter (Fåhraeus-Lindqvist effect) and exhibits a distinctive minimum at 6–7 μm. However, flow resistance in vivo in small vessels is substantially higher than predicted by in vitro viscosity data. The presence of a thick endothelial surface layer (ESL) has been proposed as the primary cause for this discrepancy. Here, a physical model is proposed for microvascular flow resistance as a function of vessel diameter and hematocrit in vivo; it combines in vitro blood viscosity with effects of a diameter-dependent ESL. The model was developed on the basis of flow distributions observed in three microvascular networks in the rat mesentery with 392, 546, and 383 vessel segments, for which vessel diameters, network architecture, flow velocity, and hematocrit were determined by intravital microscopy. A previously described hemodynamic simulation was used to predict the distributions of flow and hematocrit from the assumed model for effective blood viscosity. The dependence of ESL thickness on vessel diameter was estimated by minimizing deviations of predicted values for velocities, flow directions, and hematocrits from measured data. Optimal results were obtained with a layer thickness of ∼0.8–1 μm for 10- to 40-μm-diameter vessels and declined strongly for smaller diameters, with an additional hematocrit-dependent impact on flow resistance exhibiting a maximum for ∼10-μm-diameter vessels. These results show that flow resistance in vivo can be explained by in vitro blood viscosity and the presence of an ESL and indicate the rheologically effective thickness of the ESL in microvessels.

scholarly journals More than a biomarker: the systemic consequences of heparan sulfate fragments released during endothelial surface layer degradation (2017 Grover Conference Series)

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321774578 ◽  
Author(s):  
Kaori Oshima ◽  
Sarah M. Haeger ◽  
Joseph A. Hippensteel ◽  
Paco S. Herson ◽  
Eric P. Schmidt
Keyword(s):  
Surface Layer ◽  
Heparan Sulfate ◽  
Imaging Techniques ◽  
Endothelial Injury ◽  
Organ Injury ◽  
Endothelial Glycocalyx ◽  
Endothelial Surface Layer ◽  
Current State ◽  
Endothelial Surface

Advances in tissue fixation and imaging techniques have yielded increasing appreciation for the glycosaminoglycan-rich endothelial glycocalyx and its in vivo manifestation, the endothelial surface layer (ESL). Pathological loss of the ESL during critical illness promotes local endothelial dysfunction and, consequently, organ injury. Glycosaminoglycan fragments, such as heparan sulfate, are released into the plasma of animals and humans after ESL degradation and have thus served as a biomarker of endothelial injury. The development of state-of-the-art glycomic techniques, however, has revealed that these circulating heparan sulfate fragments are capable of influencing growth factor and other signaling pathways distant to the site of ESL injury. This review summarizes the current state of knowledge concerning the local (i.e. endothelial injury) and systemic (i.e. para- or endocrine) consequences of ESL degradation and identifies opportunities for future, novel investigations.

scholarly journals The Stage-Specific Plasticity of Descending Modulatory Controls in a Rodent Model of Cancer-Induced Bone Pain

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3286
Author(s):  
Mateusz Wojciech Kucharczyk ◽  
Diane Derrien ◽  
Anthony Henry Dickenson ◽  
Kirsty Bannister
Keyword(s):  
Dorsal Horn ◽  
Bone Pain ◽  
Early Stage ◽  
Bone Destruction ◽  
Rodent Model ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Rat Mammary Gland ◽  
Descending Control

Pain resulting from metastatic bone disease is a major unmet clinical need. Studying spinal processing in rodent models of cancer pain is desirable since the percept of pain is influenced in part by modulation at the level of the transmission system in the dorsal horn of the spinal cord. Here, a rodent model of cancer-induced bone pain (CIBP) was generated following syngeneic rat mammary gland adenocarcinoma cell injection in the tibia of male Sprague Dawley rats. Disease progression was classified as “early” or “late” stage according to bone destruction. Even though wakeful CIBP rats showed progressive mechanical hypersensitivity, subsequent in vivo electrophysiological measurement of mechanically evoked deep dorsal horn spinal neuronal responses revealed no change. Rather, a dynamic reorganization of spinal neuronal modulation by descending controls was observed, and this was maladaptive only in the early stage of CIBP. Interestingly, this latter observation corresponded with the degree of damage to the primary afferents innervating the cancerous tissue. Plasticity in the modulation of spinal neuronal activity by descending control pathways reveals a novel opportunity for targeting CIBP in a stage-specific manner. Finally, the data herein have translational potential since the descending control pathways measured are present also in humans.

scholarly journals A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Paraoxonase 1 ◽  
High Dose ◽  
Sprague Dawley ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Sprague Dawley Rats ◽  
Blood Total Cholesterol ◽  
Whole Genome Expression

The collected data have revealed the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the vascular endothelium, including vildagliptin. However, the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats were randomly divided into the following four groups: control, diabetic, diabetic + low-dose vildagliptin (10 mg/kg/d), and diabetic + high-dose vildagliptin (20 mg/kg/d). The diabetic model was created by feeding a high-fat diet for four weeks and injection of streptozotocin. Then, vildagliptin groups were given oral vildagliptin for twelve weeks, and the control and diabetic groups were given the same volume of saline. The metabolic parameters, endothelial function, and whole genome expression in the aorta were examined. After 12 weeks of treatment, vildagliptin groups showed significantly reduced blood glucose, blood total cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may inhibit angiopoietin-like 3 (Angptl3) and betaine-homocysteine S-methyltransferase (Bhmt) expression and activated paraoxonase-1 (Pon1) in the aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway of vildagliptin in vivo.

Soluble and particulate phenylethanolamine N-methyltransferase in hypothalamus of diabetic rats

1992 ◽  
Vol 263 (2) ◽  
pp. E335-E339
Author(s):  
J. E. Chappell ◽  
J. K. Stewart
Keyword(s):  
Experimental Diabetes ◽  
Diabetic Rats ◽  
Particulate Fraction ◽  
Sprague Dawley ◽  
Rat Hypothalamus ◽  
Tissue Extracts ◽  
Sprague Dawley Rats ◽  
In Vitro Response

Experimental diabetes increases total phenylethanolamine N-methyltransferase (PNMT) activity in the medulla-pons but not in the hypothalamus. In this study diabetes was induced with streptozotocin (65 mg/kg) in male Sprague-Dawley rats. Twenty-eight days after treatment there were no differences in soluble PNMT activity in the hypothalamus of diabetics and controls, but PNMT activity in a membrane-associated (particulate) fraction of hypothalamus was evaluated approximately twofold in tissues of diabetic animals compared with controls. A specific PNMT inhibitor, incubated with tissue extracts of control rats, abolished greater than 90% of particulate PNMT activity in the hypothalamus but reduced soluble PNMT activity in the hypothalamus by only 47%. These findings indicate that membrane-associated PNMT activity in rat hypothalamus differs from soluble hypothalamic PNMT in the in vitro response to an inhibitor and the in vivo response to diabetes and suggest the importance of separating subcellular hypothalamic fractions prior to assay of PNMT.

scholarly journals Renal interstitial hydrostatic pressure and sodium excretion during acute volume expansion in diabetic rats

2001 ◽  
Vol 281 (1) ◽  
pp. R239-R245 ◽  
Author(s):  
Kaushik P. Patel ◽  
Pamela K. Carmines
Keyword(s):  
Hydrostatic Pressure ◽  
Volume Expansion ◽  
Renal Denervation ◽  
Early Stage ◽  
Isotonic Saline ◽  
Diabetic Rats ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Interstitial Volume ◽  
Sprague Dawley Rats

Experiments were performed to test the hypothesis that the renal interstitial hydrostatic pressure (RIHP) response to acute volume expansion is suppressed in diabetes mellitus. Sprague-Dawley rats received streptozotocin (STZ rats; 65 mg/kg ip) or vehicle (Sham rats). Two weeks later, RIHP and Na+ excretion responses to acute graded volume expansion with isotonic saline were quantified under Inactin anesthesia (0.1 mg/kg ip). In Sham rats, acute graded volume expansion to 10% body wt produced increases in RIHP (Δ = 12.2 ± 2.4 mmHg), urine flow (Δ = 54 ± 8 μl · min−1 · g−1), and Na+ excretion (Δ = 11.5 ± 1.9 μeq · min−1 · g−1). In STZ rats, these volume expansion-induced responses were significantly blunted (RIHP by 50%, urine flow by 81%, and Na+excretion by 76%). Renal decapsulation eliminated the differences between STZ and Sham rats with regard to volume expansion-induced increases in RIHP, urine flow, and Na+ excretion. Renal denervation normalized the RIHP response to volume expansion and improved the diuretic and natriuretic responses in STZ rats. Moreover, diuretic and natriuretic responses to direct changes in RIHP (induced by renal interstitial volume expansion) were blunted in STZ rats. We conclude that diminished alterations in RIHP, as well as a reduced impact of RIHP on Na+ excretion, contribute to the impaired diuretic and natriuretic responses to acute volume expansion during the early stage of diabetes.

scholarly journals Near-Wall μ-PIV Reveals a Hydrodynamically Relevant Endothelial Surface Layer in Venules In Vivo

2003 ◽  
Vol 85 (1) ◽  
pp. 637-645 ◽  
Author(s):  
Michael L. Smith ◽  
David S. Long ◽  
Edward R. Damiano ◽  
Klaus Ley
Keyword(s):  
Surface Layer ◽  
Endothelial Surface Layer ◽  
Endothelial Surface ◽  
Near Wall

Regulation of myocardial lipoprotein lipase activity by diabetes and thyroid hormones

1994 ◽  
Vol 72 (11) ◽  
pp. 1259-1264 ◽  
Author(s):  
Limin Liu ◽  
David L. Severson
Keyword(s):  
Thyroid Hormones ◽  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Hormone Treatment ◽  
Diabetic Rats ◽  
Lipoprotein Lipase Activity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Perfused Hearts

Administration of streptozotocin (100 mg/kg) to adult Sprague–Dawley rats reduced both functional (heparin releasable) lipoprotein lipase activity in perfused hearts and total and heparin-releasable lipoprotein lipase activity in isolated cardio-myocytes, and produced a hypothyroid state (decreased plasma levels of triiodothyronine and thyroxine). Administration of replacement doses of triiodothyronine (3 or 10 μg/kg for 3 days) to diabetic rats normalized heparin-releasable lipoprotein lipase activity in perfused hearts, but the depressed lipoprotein lipase activity in cardiomyocytes from diabetic hearts was unchanged by in vivo thyroid hormone treatment. However, hypothyroidism in thyroidectomized rats did not alter lipoprotein lipase activity in either perfused hearts or isolated cardiomyocytes. Therefore, thyroid hormones may interact with some other factor(s) in this acute, insulin-deficient model of diabetes to selectively regulate functional, heparin-releasable lipoprotein lipase activity in perfused hearts.Key words: diabetes, hypothyroidism, lipoprotein lipase, perfused hearts, cardiomyocytes.

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