Permeability to albumin in isolated coronary venules

1993 ◽  
Vol 265 (2) ◽  
pp. H543-H552 ◽  
Author(s):  
Y. Yuan ◽  
W. M. Chilian ◽  
H. J. Granger ◽  
D. C. Zawieja
Keyword(s):  
Permeability Coefficient ◽  
Filtration Rate ◽  
Intraluminal Pressure ◽  
Apparent Permeability ◽  
Filtration Pressure ◽  
Diffusive Permeability ◽  
Apparent Permeability Coefficient ◽  
Chemical Conditions ◽  
Physical And Chemical ◽  
Intravascular Pressure

This study reports measurements of albumin permeability in isolated coronary venules. The isolated microvessel technique allows the quantification of transmural exchange of macromolecules under tightly controlled physical and chemical conditions. Transvenular exchange of albumin was studied in isolated coronary venules during alterations in filtration rate caused by changes in intravascular pressure. The apparent permeability coefficient of albumin (Pa) at an intraluminal pressure of 11 cmH2O was 3.92 +/- 0.43 x 10(-6) cm/s. Elevating intraluminal pressure to 16 and 21 cmH2O increased Pa to 5.13 +/- 0.57 x 10(-6) and 6.78 +/- 0.66 x 10(-6) cm/s, respectively. Calculation of the true diffusive permeability coefficient of albumin (Pd) at zero filtration rate was 1.54 x 10(-6) cm/s. The product of hydraulic conductance (Lp) and (1 - sigma), where sigma is the solute reflection coefficient, was 3.25 x 10(-7) cm.s-1 x cmH2O-1. At a net filtration pressure of 4-5 cmH2O, diffusion accounts for > 60% of total albumin transport across the venular wall. Transmural albumin flux is very sensitive to filtration rate, rising 6.7% for each cmH2O elevation of net filtration pressure. At 11 cmH2O net filtration pressure, convection accounts for nearly 70% of net albumin extravasation from the venular lumen. We suggest that the isolated coronary venule is a suitable preparation for the study of solute exchange in the heart.

scholarly journals Development and In Vitro Evaluation of a Mucoadhesive Oral Deliverv System for Antisense Oliaonucleotides

2003 ◽  
Vol 71 (3) ◽  
pp. 165-177 ◽  
Author(s):  
Andreas Bernkop-Schnürch ◽  
Julia Telsnig ◽  
Margit Hornof
Keyword(s):  
Delivery System ◽  
Permeability Coefficient ◽  
Enzymatic Degradation ◽  
Phosphorothioate Oligonucleotide ◽  
Apparent Permeability ◽  
Release Studies ◽  
Apparent Permeability Coefficient ◽  
Permeation Studies ◽  
Membrane Bound

It was the aim of this study to develop an oral phosphorothioate oligodeoxynucleotide (PS-ODN) drug delivery system and to evaluate its properties in vitro. Results demonstrated that the 16-mer phosphorothioate oligonucleotide used was completely stable towards enzymatic degradation by secreted and membrane bound intestinal enzymes. Permeation studies with freshly excised intestinal mucosa showed a comparatively high uptake of the PS-ODN with an apparent permeability coefficient (Papp) of 8.35 ± 1.24 x 10-6 cm/sec. The PS-ODN was incorporated in a poly(acrylic acid)-cysteine carrier matrix system exhibiting high cohesive and mucoadhesive properties. Release studies demonstrated that a controlled and sustained PS-ODN release out of this delivery system could be achieved. Because of these features, the dosage form developed within this study seems to represent a promising novel tool for oral PS-ODN delivery.

Histamine increases venular permeability via a phospholipase C-NO synthase-guanylate cyclase cascade

1993 ◽  
Vol 264 (5) ◽  
pp. H1734-H1739 ◽  
Author(s):  
Y. Yuan ◽  
H. J. Granger ◽  
D. C. Zawieja ◽  
D. V. DeFily ◽  
W. M. Chilian
Keyword(s):  
Phospholipase C ◽  
Guanylate Cyclase ◽  
Permeability Coefficient ◽  
Direct Action ◽  
No Synthase ◽  
Constant Flow ◽  
Apparent Permeability ◽  
Apparent Permeability Coefficient ◽  
Synthase Inhibitor ◽  
Ly 83583

In this study, we hypothesized that histaminergic increases in venular permeability result from a cascade triggered by activation of phospholipase C (PLC), inducing the synthesis of nitric oxide (NO) and activating guanylate cyclase. The apparent permeability coefficient to albumin (Pa) was measured in isolated porcine coronary venules subjected to constant flow and hydrostatic and oncotic pressures. Histamine (2.5, 5, and 10 microM) transiently and progressively increased Pa. The PLC inhibitor 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC; 100 microM) decreased baseline permeability and abolished the effect of histamine. The NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10 microM) and the guanylate cyclase inhibitor 6-anilinoquinoline-5,8-quinone (LY 83583; 10 microM) also blocked the histamine-induced hyperpermeability. L-Arginine (3 mM) reversed the inhibition by L-NMMA. NG-monomethyl-D-arginine did not influence the effect of histamine. Furthermore, sodium nitroprusside (10 microM) augmented Pa by two- to threefold; this effect was blocked in the presence of LY 83583 but not altered in the presence of NCDC. The results suggest that histamine increases coronary venular permeability by a direct action on the venular endothelial cells through a PLC-NO synthase-guanylate cyclase-signaling cascade.

Active amino acid absorption by proximal convoluted and proximal straight tubules

1979 ◽  
Vol 236 (2) ◽  
pp. F149-F162 ◽  
Author(s):  
D. W. Barfuss ◽  
J. A. Schafer
Keyword(s):  
Permeability Coefficient ◽  
Rabbit Kidney ◽  
Apparent Permeability ◽  
Nonlinear Fitting ◽  
Luminal Membrane ◽  
Straight Tubules ◽  
Apparent Permeability Coefficient ◽  
Active Amino Acid ◽  
The Mean ◽  
The Relationship

Transport of glycine and alpha-aminoisobutyric acid (AIB) was studied in proximal convoluted (PCT) and proximal straight (PST) tubules isolated from rabbit kidney. In both segments, unidirectional lumen-to-bath fluxes (J1 leads to b) (pmol min-1mm-1) of glycine and AIB exceeded corresponding bath-to-lumen fluxes (Jb leads to 1), which demonstrated that both were actively absorbed. During J1 leads to b measurements, intracellular concentrations of both amino acids were greater than the luminal concentration, indicating that the site of active transport was the luminal membrane. Replacement of Na+ by choline in both perfusate and bath (PCT) or perfusate alone (PST) reduced J1 leads to b for glycine to equal Jb leads to 1. Nonlinear fitting of the relationship between J1 leads to b and the mean luminal glycine concentration according to Michaelis-Menten kinetics gave Jmax values of 28.5 (PCT) and 2.5 (PST) pmol min-1 mm-1, and Km values of 11.8 (PCT) and 0.7 (PST) mM. There was a parallel, Na+-independent, nonsaturable component of J1 leads to b characterized by an apparent permeability coefficient of 0.19 micron/s in the PCT and 0.04 micron/s in the PST.

Base secretion in rat distal colon: ionic requirements

1990 ◽  
Vol 258 (6) ◽  
pp. G825-G832 ◽  
Author(s):  
G. M. Feldman ◽  
J. D. Koethe ◽  
R. L. Stephenson
Keyword(s):  
Permeability Coefficient ◽  
Distal Colon ◽  
Secretory Component ◽  
Bathing Solution ◽  
Apical Surface ◽  
Apparent Permeability ◽  
Rat Distal Colon ◽  
Apparent Permeability Coefficient ◽  
Diffusive Component ◽  
Active Base

To evaluate the ionic requirements of colonic base secretion, segments of rat distal colon were studied under short-circuited conditions. Net base flux was composed of an active secretory component and a diffusive component. Studied in the absence of a transepithelial HCO3- concentration gradient, active base secretion was dependent on the HCO3- concentration of the bathing solution but was not influenced by the CO2 tension or pH. Base secretion appeared to saturate with a Km of 33 +/- 9 mM and was inhibited by ouabain. The diffusive component was characterized by an apparent permeability coefficient to HCO3- of 8.9 +/- 0.9 x 10(-6) cm/s. In addition to requiring HCO3- on the serosal surface, net base secretion was inhibited by reducing the Na+ concentration in the serosal medium and the Cl- concentration in the mucosal medium. These data suggest that colonic base secretion involves HCO3- entry across the basolateral surface, energized by the Na+ gradient, and HCO3- exit across the apical surface in exchange for Cl-.

Solvent drag of LDL across mammalian endothelial barriers with increased permeability

1995 ◽  
Vol 268 (5) ◽  
pp. H1982-H1991 ◽  
Author(s):  
J. C. Rutledge ◽  
F. E. Curry ◽  
P. Blanche ◽  
R. M. Krauss
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Effective Radius ◽  
Solvent Drag ◽  
Apparent Permeability ◽  
Ldl Transport ◽  
Diffusive Permeability ◽  
Endothelial Barriers ◽  
Mean Pressure ◽  
Apparent Permeability Coefficient

We investigated the mechanisms of hamster low-density lipoprotein (LDL) transport across the endothelial barrier in individually perfused venular microvessels in hamster mesentery. These experiments are the first to use microperfusion techniques and quantitative fluorescence microscopy to investigate LDL transport across mammalian microvessel endothelium. The apparent permeability coefficient for hamster LDL, PsLDL, rose from 2.7 x 10(-7) cm/s at control to 23.2 x 10(-7) cm/s at the peak of the biphasic increase in microvessel permeability after exposure of the vessels to 100 microM histamine. Close to the peak, PsLDL rose 1.85 x 10(-7) cm/s for every centimeter of H2O increase in hydrostatic pressure. Thus, at a mean pressure of 11.3 cmH2O, 90% of the LDL flux was coupled to transendothelial water flow by a solvent drag mechanism. The corresponding solvent drag reflection coefficient for hamster LDL was estimated to be approximately 0.8. These results are consistent with sieving hamster LDL (effective radius 14.9 nm) through equivalent pores of approximately 22 nm radius. Similar results were found with human LDL (effective radius 13.2 nm) in hamster microvessels. The results provide a bridge between studies of LDL transport across cultured endothelial barriers, where high diffusive permeability coefficients to LDL may obscure the contributions of solvent drag, and studies in whole animals, where the consequences of sieving of LDL at the vessel wall, even in the high permeability state, have not received much attention.

Factors determining superficial nephron filtration in the mature, growing rat

1977 ◽  
Vol 232 (2) ◽  
pp. F97-F104
Author(s):  
B. J. Tucker ◽  
R. C. Blantz
Keyword(s):  
Body Weight ◽  
Glomerular Filtration Rate ◽  
Permeability Coefficient ◽  
Wistar Rats ◽  
Filtration Rate ◽  
Plasma Expansion ◽  
Glomerular Permeability ◽  
Filtration Pressure ◽  
Pressure Equilibrium ◽  
Growing Rat

Factors that determine and cause an increased glomerular filtration rate in superficial nephrons (sngfr) in the mature, growing rat were examined in 39 Munich-Wistar rats, ranging from 93 to 335 g in body weight, from 40 to 140 days in age, and in sngfr, from 15 to 78 nl/min. Hydrostatic pressure gradient (delta P) from glomerular capillary (PG) to Bowman's space (Pt) was measured in surface glomeruli and pertinent oncotic pressures (pi) by microprotein methods. Isoncotic plasma expansion (PV) prevented filtration-pressure equilibrium (EFP) and permitted calculation of glomerular permeability coefficient (LpA) where sngfr = EFP-LpA, and EFP = delta P - pi. Increased sngfr correlated best with nephron plasma flow (rpf) (r = 0.81, P less than 0.001) and LpA (r = 0.71, P less than 0.001). The rpf increased because of parallel reductions in afferent and efferent resistances (slope = 0.89 +/- 0.09, r = 0.86, P less than 0.001), which also produced a constancy of PG and deltaP with growth. The ratio of rpf to LpA remained constant with growth permitting EFP to remain relatively unchanged (r = 0.14, P greater than 0.4). The increase in LpA should permit filtration-pressure equilibrium to persist in the hydropenic rat in spite of increases in rpf with growth. deltaP was constant with increasing age and therefore did not contribute to the increase in sngfr.

scholarly journals Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 134 ◽  
Author(s):  
López-Yerena ◽  
Vallverdú-Queralt ◽  
Mols ◽  
Augustijns ◽  
Lamuela-Raventós ◽  
...  
Keyword(s):  
Permeability Coefficient ◽  
Oral Absorption ◽  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Rat Plasma ◽  
Apparent Permeability ◽  
Time Curve ◽  
In Situ Perfusion ◽  
Apparent Permeability Coefficient

Oleocanthal (OLC), a phenolic compound of extra virgin olive oil (EVOO), has emerged as a potential therapeutic agent against a variety of diseases due to its anti-inflammatory activity. The aim of the present study is to explore its in vivo intestinal absorption and metabolism. An in situ perfusion technique in rats was used, involving simultaneous sampling from the luminal perfusate and mesenteric blood. Samples were analysed by UHPLC–MS–MS for the presence of oleocanthal (OLC) and its metabolites. OLC was mostly metabolized by phase I metabolism, undergoing hydration, hydrogenation and hydroxylation. Phase II reactions (glucuronidation of hydrogenated OLC and hydrated metabolites) were observed in plasma samples. OLC was poorly absorbed in the intestine, as indicated by the low effective permeability coefficient (2.23 ± 3.16 × 10−5 cm/s) and apparent permeability coefficient (4.12 ± 2.33 × 10−6 cm/s) obtained relative to the values of the highly permeable reference compound levofloxacin (LEV). The extent of OLC absorption reflected by the area under the mesenteric blood-time curve normalized by the inlet concentration (AUC) was also lower than that of LEV (0.25 ± 0.04 vs. 0.64 ± 0.03, respectively). These results, together with the observed intestinal metabolism, suggest that OLC has a moderate-to-low oral absorption; but higher levels of OLC are expected to reach human plasma vs. rat plasma.

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