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PubMed2006

Effects of serum of the rats ventilated with high tidal volume on endothelial cell permeability and therapeutic effects of ulinastatin.

BACKGROUND: With the widespread use of ventilators in treating critically ill patients, the morbidity of ventilator-induced lung injury (VILI) is increasing accordingly. VILI is characterized by a considerable increase in microvascular leakiness and activation of inflammatory processes. In this study we investigated the effects of inflammatory mediators in VILI rat serum on endothelial cytoskeleton and monolayer cellular permeability, as well as the therapeutic effect of ulinastatin, to explore the pathogenesis and the relationship between biotrauma and lung oedema induced by VILI. METHODS: Thirty healthy male Sprague-Dawley rats were randomly divided into three groups: group A (normal tidal volume ventilation), group B (high tidal volume ventilation) and group C (high tidal volume ventilation plus ulinastatin). The serum of each rat after ventilation was added to endothelial cell line ECV-304 medium for two hours to observe the effects of serum and/or ulinastatin on endothelial fibrous actin and permeability. RESULTS: Compared to rats ventilated with normal tidal volume, serum of rats ventilated with high tidal volume caused a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity at the peripheral filament bands and formation of the long and thick stress fibres in the centre resulting in endothelial contraction and higher permeability. Prior treatment with ulinastatin lessened the above changes significantly. The changes of permeability coefficient of endothelial permeability after group A, B or C rats serum stimulation were (6.95 +/- 1.66)%, (27.50 +/- 7.77)% and (17.71 +/- 4.66)% respectively with statistically significant differences (P < 0.05) among the three groups. CONCLUSIONS: The proinflammatory mediators in the serum of the rats given high tidal volume ventilation increases endothelial permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin lessens the permeability by inhibiting of proinflammatory mediators.

Actins↗
PubMed1991

Cadmium as a tool for studying calcium-dependent cation permeability of the human red blood cell membrane.

Three Ca(2+)-dependent procedures known to increase cation permeability of red blood cell membranes were tested with Cd2+ ions which equal Ca2+ ions both in their charge and the crystal radius, 1. Increase of non-selective permeability for monovalent cations by incubating the red cells in a Ca(2+)-free sucrose medium. Addition of Cd2+ to the suspension of leaky cells failed to restore the initial impermeability of the red cell membrane while a repairing effect of Ca2+ was evident both in the presence and absence of Cd2+. Thus, in low electrolyte medium, Cd2+ could neither mimic Ca2+, nor prevent the latter from interacting with membrane structures which control cation permeability. 2. Increase of the K(+)-selective permeability by propranolol plus Ca2+. Cd2+ added to a Ca(2+)-free Ringer type medium containing propranolol enhanced K+ permeability similar to that obtained with Ca2+. No changes of membrane permeability could be detected in the presence of 0.5 mmol/l Cd2+ in absence of propranolol. The Cd(2+)-stimulated K+ channels were different from those induced by Ca2+. They proved to be insensitive to quinine, exhibited a low K+/Na+ selectivity, and showed no tendency to self-inactivation. 3. Stimulation of K+ permeability by electron donors plus Ca2+. Substitution of Ca2+ by Cd2+ yielded results similar to those obtained with propranolol. The ability of Cd2+ to overtake the role of Ca2+ appears to depend on the system studied. It supplies information allowing to distinguish between the diverse Ca(2+)-dependent systems in cell membranes.

Ascorbic Acid↗
PubMed1990

Ability of human T lymphocytes to adhere to vascular endothelial cells and to augment endothelial permeability to macromolecules is linked to their state of post-thymic maturation.

The accumulation of mononuclear cells at sites of chronic inflammation is dependent on a number of factors including localized adherence of lymphocytes to vascular endothelial cells (EC), cytokine-mediated increased adhesiveness of endothelium, chemotactic factors and endothelial permeability. The present study investigates two of the above attributes of lymphocyte-EC interaction: namely, the ability of maturationally distinct subpopulations of human T lymphocytes to adhere to vascular EC and to increase vascular endothelial permeability to macromolecules in an in vitro model. Thus, human T lymphocytes were separated into CD4+ CD8-helper/inducer, CD4- CD8+ cytotoxic/suppressor, CD29+ CD45RA- CD45RO+ memory, and CD29- CD45RA+ CD45RO- naive/virgin T subpopulations, were activated with PHA and PMA, and then examined for their adherence to EC and also for their effect on endothelial permeability. Upon activation, cells within each of the above four subpopulations exhibited increased adherence to EC. In contrast, resting CD29+ CD45RA- CD45RO+ memory T lymphocytes exhibited two to three times greater ability to adhere to EC than their CD29- CD45RA+ CD45RO- naive/virgin counterparts. Consistent with their increased adherence to EC, CD29+ CD45RO+ memory T lymphocytes, when activated, significantly increased endothelial permeability to albumin. Although activated CD45RA+ naive T lymphocytes exhibited increased adherence to EC, these cells failed to increase significantly endothelial permeability. Similar to their polyclonal counterparts, Ag-specific CD4+ CD29+ CD45RO+ T cell clones, but not their actively released mediators, also increased endothelial permeability via a noncytolytic mechanism(s). This ability of CD29+ CD45RO+ memory T lymphocytes to augment endothelial permeability may facilitate their transendothelial migration into extravascular space. These observations may provide additional insights into molecular mechanism(s) underlying pathophysiology of localized chronic inflammatory responses in general and more specifically selective accumulation of CD29+/CD45RO+ memory T lymphocytes at sites of chronic inflammation such as rheumatoid synovium.

Antigens, CD↗
PubMed1990

Effect of leukotriene receptor antagonists on vascular permeability during endotoxic shock.

Evidence has accumulated that sulfidopeptide leukotrienes are significant pathogenic mediators of certain hematologic and hemodynamic sequelae of endotoxic shock. In the present study, the effects of a selective LTD4/E4 receptor antagonist, LY171883 (LY), or a selective LTD4 receptor antagonist, SKF-104353 (SKF), were assessed on splanchnic and pulmonary localization of 99mTechnetium-labeled human serum albumin (99mTc-HSA) in acute endotoxic shock in the rat. Dynamic gamma camera imaging of heart (H), midabdominal (GI), and lung regions of interest generated time activity curves for baseline and at 5-35 min after Salmonella enteritidis endotoxin (10 mg/kg, i.v.). Slopes of GI/H and lung/H activity (permeability index, GI/H or lung/H X 10(-3)/min) provided indices of intestinal and lung localization. Rats received LY (30 mg/kg, i.v.), LY vehicle (LY Veh), SKF (10 mg/kg), or SKF vehicle (SK Veh) 10 min prior to endotoxin or endotoxin vehicle. In rats receiving the LY Veh and endotoxin (n = 8) or SKF Veh and endotoxin (n = 12), the splanchnic permeability indices to 99mTc-HSA were increased 11.2-fold and 5.1-fold, respectively (P less than 0.05) compared to vehicle control groups not given endotoxin (n = 5). Pulmonary permeability index for 99mTc-HSA was increased (P less than 0.05) to a lesser extent (3.2-fold) by endotoxin compared to vehicle controls. Pretreatment with SKF reduced the mesenteric permeability index to control levels (P less than 0.05) during the 5-35 min time interval post-endotoxin. LY reduced the mesenteric permeability index by 70%. Pulmonary relative permeability to 99mTc-HSA was not affected by LY pretreatment. Both splanchnic and lung relative permeability to the isotope was transient; at 135-225 min post-endotoxin, splanchnic localization of 99mTc-HSA (n = 4) was not significantly different from vehicle controls in these vascular beds. Relative localization of 99mTc-labeled red blood cells (RBC) in the splanchnic or lung region was not significantly altered by endotoxin (n = 7) or LY pretreatment (n = 6) compared to vehicle controls (n = 6). In additional studies, small intestinal luminal content of 99mTc-HSA and 111Indium (In)-labeled RBC were determined after i.v. administration of the isotopes, in a 4 cm segment of the upper small bowel. Radioactivity in the luminal lavage was normalized to activity in blood of the same animal. Endotoxin at 2 hr induced a 2.3-fold increase transluminal leakage of 99mTc-HSA (n = 5; P less than 0.03) compared to LY Veh (n = 5) or control (n = 5) rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetophenones↗
PubMed1990

Thromboxane A2-mimetics are potent microvascular permeability factors in the conjunctiva.

These studies demonstrate that the thromboxane (Tx) A2 mimetics U-46619, U-44069 and carbocyclic-TxA2 elicit a microvascular permeability response in the conjunctiva. U-46619 and U-44069 are among the most potent microvascular permeability factors described to date for the conjunctiva; their potency is exceeded only by that reported for leukotrienes D4 and E4. The conjunctival microvascular permeability response to U-46619 was inhibited by the TxA2-antagonists daltroban (BM 13505) and SQ 29548. Prostaglandin (PG) D2 also increased conjunctival microvascular permeability, but was less potent than U-46619 and far less susceptible to pretreatment with daltroban or SQ 29548. PGE2, PGF2 alpha and the prostacyclin analog carbocyclin did not increase conjunctival microvascular permeability. It appears that the conjunctiva exhibits a unique microvascular permeability response to TxA2-mimetics: this view is experimentally supported by the absence of a cutaneous microvascular permeability response to U-46619, U-44069 and carbocyclic-TxA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMedDate not supplied

Evaluation of capillary permeability and microcirculation in patients with chronic venous hypertension treated with venoruton by the vacuum suction chamber (VSC) device and laser-Doppler flowmetry.

A new system to study capillary permeability, the VSC (vacuum suction chamber) device has been developed to evaluate the variations of capillary permeability in postphlebitic limbs. The VSC device produces by negative pressure [obtained in a plastic chamber applied to the skin at the perimalleolar region] a wheal which disappears in normals in less than one hour. In twelve patients with moderate [superficial] venous hypertension and in twelve patients with postphlebitic limbs the time of disappearance of the wheals was significantly longer in comparison with ten normal limbs. There was also a significantly increased time of disappearance of the wheals in postphlebitic legs in comparison with those with superficial incompetence. The validation of the VSC technique with venous occlusion plethysmography (VOP) showed that the increase of time of disappearance of the wheals is well correlated with the increase of capillary permeability demonstrated by VOP. After 2 weeks treatment with Venoruton (at the dosage of 1000 mg t.i.d.) the time of disappearance of the wheal was significantly reduced in both groups of patients (while it was unchanged in normals). Laser-Doppler parameters used together with the VSC device to evaluate the microcirculatory changes associated with an altered capillary permeability also showed a significant improvement of the laser-Doppler parameters after treatment. In conclusion there is evidence by the VSC device that capillary permeability [which is abnormally increased] in chronic venous hypertension is improved [decreased] after treatment for two weeks with Venoruton. This study demonstrated also the efficacy of the VSC device to study capillary permeability and the effects of drugs active on capillary permeability.

Adult↗
PubMed1987

Role of bradykinin generating and degrading systems in the vascular permeability response induced with kaolin in rats.

We investigated how bradykinin mediates inflammatory reactions in rats, via measurements of bradykinin by enzyme immunoassay method in inflammatory tissue fluids. Vascular permeability was increased markedly during the first 10 min and then declined quickly after the infusion of a kaolin suspension (10 mg/ml) in 0.8% carboxymethl-cellulose solution into an air pouch formed on the back of rats. Bradykinin in the exudate reached a maximum 5 min after the challenge and then decreased quickly. Local treatment with DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, an inhibitor of kininase I, and captopril, an inhibitor of kininase II in the first 10-min period, each enhanced the vascular permeability increase accompanied by the elevation of the bradykinin level, whereas soybean trypsin inhibitor, a plasma kallikrein inhibitor, lowered both vascular permeability and bradykinin. When applied in the period of 3.5 to 4 hr after the challenge, only the kininase II inhibitor was effective in elevating both vascular permeability and the bradykinin level, whereas soybean trypsin inhibitor was ineffective on vascular permeability. A bradykinin-degrading activity appeared in the exudate as early as 10 min after the challenge. These results suggest that bradykinin plays an essential role for the sudden rise of the vascular permeability observed immediately after the infusion of kaolin suspension. In the later stage (3.5-4 hr), bradykinin level remained below the assay limit of 0.07 ng/ml in spite of its active generation, presumably because of its rapid degradation by the kininases, although it still played a definite role in the vascular permeability increase.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Characterization of Ca2+-stimulated secretion in permeable GH3 pituitary cells.

In this report, the secretory response to Ca2+ in GH3 rat pituitary cells permeabilized by electric field discharge has been compared in both magnitude and Ca2+ sensitivity to prolactin (PRL) release from intact GH3 cells. The half-maximally effective [Ca2+] for stimulating PRL release in permeable cells was approximately 0.5 microM, and maximal stimulation was obtained at 3-10 microM Ca2+. The magnitude of Ca2+ stimulation in permeable cells was in the same range as that obtained from an equal number of intact cells stimulated by depolarizing K+. Moreover, the Ca2+ sensitivity of PRL release in intact GH3 cells (measured by Quin 2 fluorescence) closely resembled the Ca2+ sensitivity determined in permeable cells. Release of a sulfated proteoglycan whose release is stimulated by secretagogues in intact cells was stimulated by Ca2+ in permeable cells with the same Ca2+ sensitivity as for PRL release. Maximal Ca2+ stimulation of PRL release in permeable cells required the addition of MgATP. Other energy sources (ADP, GTP, and inorganic phosphate) also supported Ca2+-stimulated secretion but were less effective. The above results indicated that PRL release from permeable cells resembles the physiological process in intact cells. The permeable cell system should prove useful in investigating the mechanism mediating the effect of Ca2+ on secretion, although our studies with pharmacological agents have so far proved inconclusive. Among calmodulin antagonists tested, only trifluoroperazine inhibited Ca2+-stimulated secretion, whereas pimozide and calmidazolium did not.

Adenosine Triphosphate↗
PubMed1986

Sucrose permeability of the blood-retinal and blood-brain barriers. Effects of diabetes, hypertonicity, and iodate.

The permeabilities of the blood-retinal (BRB) and blood-brain (BBB) barriers to sucrose were determined simultaneously using an intravenous injection technique in the rat. The method involved direct sampling of retinal tissue in order to avoid errors caused by sucrose penetration across other components of the blood-ocular barrier. The permeability X surface area (PS) product for the BRB was approximately four times greater than for the BBB. Intracarotid infusion of a hypertonic arabinose solution resulted in a dose-dependent increase in the permeability of both barrier systems. In contrast, 24 hr after treatment of animals with iodate, the PS product for the BRB but not the BBB was increased. The permeability of the blood-retinal barrier to sucrose was measured in normal and 2-, 6-, and 20-week streptozocin diabetic rats. The BRB was unaffected at 2 and 6 weeks of diabetes, and showed only a small increase in permeability at 20 weeks. Our results suggest that alterations in the blood-ocular barrier in early diabetes do not result from an increased passive permeability of the BRB. The method described should permit direct comparison of BRB and BBB permeabilities to a variety of compounds under various conditions.

Animals↗
PubMed1987

The membrane attack complex of complement induces permeability changes via thresholds in individual cells.

Flow cytometry was used to quantify the fluorescence of propidium iodide in rat polymorphonuclear leucocytes (PMN) attacked by the membrane attack complex (MAC) in order to establish the existence of permeability and lytic thresholds in individual cells, a 'threshold' being defined as a cellular event involving the rapid transition of cells from one state to another under physiological conditions. Activation of the complement pathway resulted in PMN being attacked by MAC within 5 min. Approximately 30-40% of the cell population subsequently became permeable to small molecules and macromolecules. Individual PMN passed through 'thresholds' of cell permeability and cell lysis, or recovered from complement attack at different times. In the flow cytometer, three distinct populations of PMN were identified: cells that had recovered before the permeability 'threshold', cells that had recovered after the permeability 'threshold' but before the lytic 'threshold', and cells that failed to recover from complement attack. Individual PMN attacked by MAC passed through permeability and lytic thresholds at different times after an initial lag of 7.5 +/- 2.5 min and 11.5 +/- 1.0 min, respectively. Adenosine, an activator of adenylate cyclase, inhibited removal of MAC from the cell surface. Consequently, more cells passed through the permeability and lytic 'thresholds', resulting in an increased percentage of lysed cells.

2-Chloroadenosine↗
PubMed1984

The permeability of uncoupled heart mitochondria to potassium ion.

Isolated heart mitochondria retain matrix K+ in a K+-free medium and exchange matrix 42K+ with external K+ only slowly. This low permeability to K+ is maintained when the proton motive force is dissipated by addition of an uncoupler, but can be increased markedly in uncoupled mitochondria when (a) NADPH becomes oxidized and (b) a Ca2+ chelator or ruthenium red is added (Jung, D. W., and Brierley , G. P. (1981) J. Biol. Chem. 256, 10490-10496). This latter requirement suggests that decreased Ca2+ binding or alteration of the Ca2+ uniporter may be involved in the induction of permeability to K+ in these mitochondria. The present studies establish that La3+ (k0.5 = 1.8 nmol X mg-1 of protein) also induces K+ permeability in uncoupled mitochondria in which NADPH has been oxidized. The amount of net K+ loss or passive 42K+/K+ exchange induced by La3+ corresponds to that produced by ruthenium red or EGTA and appears to vary from preparation to preparation as a function of the endogenous adenine nucleotide (AN) content of the mitochondria. The permeability to K+ induced by all three reagents is increased by depletion of endogenous AN with PPi and strongly inhibited by low levels of exogenous AN. The optimum passive permeability to K+ develops at pH 7.5, is inhibited by Nupercaine , quinine, and dicyclohexylcarbodiimide, and is increased in a sucrose, as opposed to a KCl medium. The increased permeability to K+ appears to result from the opening of one or more K+-conducting uniport pathways, rather than K+/H+ exchange. Since Ca2+ efflux remains sensitive to ruthenium red when K+ efflux is induced, it seems unlikely that the Ca2+ uniporter itself can provide a pathway for K+ flux. The presence of such latent pathways for passive K+ permeability must be considered when defining the properties of the putative K+/H+ antiporter and during isolation and reconstitution protocols involving mitochondrial K+ transport components.

Adenosine Diphosphate↗
PubMed1984

Guinea pig plasma kallikrein as a vascular permeability enhancement factor. Its dependence on kinin generation and regulation mechanisms in vivo.

Plasma kallikrein (mol wt 80,000) was purified from guinea pig plasma, and it caused vascular permeability enhancement when injected into guinea pig skin. The activity had a linear relationship to the logarithm of kallikrein concentrations from 5 X 10(-9) M to 5 X 10(-6) M and was blocked by immunopurified anti-prekallikrein F(ab')2 rabbit antibody and soybean trypsin inhibitor. Carboxypeptidase B(1.7 units), a kinin-destructive enzyme, decreased the permeability activity to 1/20, while SQ 20,881 (10(-6) M), an inhibitor to a kinin-destructive enzyme, augmented the activity 5.4-fold. These results suggested that the permeability activity of kallikrein was performed finally through kinin generation in the skin. The permeability activity was short-lasting, and was completely blocked by a kallikrein inhibitor purified from guinea pig plasma, suggesting the presence of a down-regulation system for the permeability activity in vivo. Prostaglandin E2 (25 ng), a hyperemia inducer in microcirculation, augmented the permeability activity 12-fold, suggesting the presence of an up-regulation system in vivo. Accordingly, it was assumed that kallikrein-kinin system might play a role as a vascular permeability enhancement system in guinea pig skin.

Animals↗
PubMed1984

Measurement of retinal permeability to sodium fluorescein in vitro.

Fluorescein permeabilities of isolated dog retinal pigment epithelium (RPE)-choroid and sensory retina were measured individually. Retina to choroid (outward) permeability of sodium fluorescein was significantly larger than choroid to retina (inward) permeability at RPE-choroid under both open- and short-circuit conditions. Outward permeability was decreased by the addition of 10(-3) M KCN and of 10(-4) M probeneside but was not affected by 10(-6) M ouabain. These drugs decreased transepithelial potential and short-circuit current. No directional difference of fluorescein permeability for sensory retina was found. Active transport of fluorescein across RPE from retina to choroid is suggested. Fluorescein permeability of sensory retina was larger than inward but less than outward permeability of RPE-choroid. The result indicates that the sensory retina acts as a diffusion barrier for sodium fluorescein.

Animals↗
PubMed1984

[Local blood flow and capillary permeability in the experimental meningeal carcinomatosis].

Local blood flow and capillary permeability of the rats with meningeal carcinomatosis were studied with macroautoradiography, and relationship between blood flow, permeability and effects of chemotherapy is discussed. Experimental meningeal carcinomatosis was induced in the Wistar rats by inoculating Walker 256 tumor into cisterna magna. One to 12 days after inoculation, rats were used for measurements of blood flow (by 14C- iodoantipyrine) and capillary permeability (by 14C-alpha-aminoisobutyric acid). Images of autoradiography and corresponding histological appearances were analyzed. In the early stage of tumor growth (2 to 3 days after inoculation), a few layers of tumor cells were identified in the ambient cistern. Blood flow in the vicinity of the tumor cell layer was noted, but no increase in capillary permeability was found. In the middle stage of tumor growth (3 to 5 days after inoculation), 10 to 20 layers of the tumor cell was noted in the ambient cistern. Blood flow in the tumor was evident and capillary permeability began to increase. In the late stage of tumor growth (6 to 12 days after inoculation), a mass of the tumor cells was noted in the ambient cistern. In this stage, blood flow in the tumor was similar to that of cerebral gray matter and capillary permeability increased markedly. Brain adjacent to the tumor also showed increase in capillary permeability. The result correlated well to the previous result of experimental chemotherapy. Form those data, lipid soluble drugs which cross blood-brain barrier readily are recommended for the early stage of meningeal carcinomatosis, and water soluble drugs which has limitations to cross blood-brain barrier can not be recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

[The mechanism of anti-vascular permeability of 2-(2-fluoro-4-biphenylyl) propionic acid(Flurbiprofen) (author's transl)].

Effect of 2-(2-fluoro-4-biphenylyl) propionic acid(Flurbiprofen, FP-70) on increased vascular permeability was studied using the potentiation of bradykinin-induced vascular permeability by prostaglandin in the guinea pig skin, as the test system. Prostaglandin E1 or E2 (1 microgram/site) alone did not show increased vascular permeability but did enhance the effect of various concentrations of bradykinin when concomitantly applied, whereas prostaglandin F2 alpha did not potentiate the effect of bradykinin on vascular permeability. Arachidonic acid (100 microgram/site) had no effect on vascular permeability when injected alone or in combination with bradykinin. However, arachidonic acid enhanced the effect of bradykinin when given 30 min before bradykinin. FP-70 had no inhibitory effect on prostaglandin E1 potentiation of bradykinin-induced vascular permeability. On the other hand, FP-70 completely abolished the enhancement of the effect of bradykinin by arachidonic acid. These results strongly suggest that anti-vascular permeability action of FP-70 may be due to inhibition of prostaglandin synthetase. Indomethacin and acetylsalicylic acid also exhibit similar effects. However, the inhibitory effect of FP-70 was 12.5 and 166.7 times as potent as indomethacin and acetylsalicylic acid, respectively.

Animals↗
PubMed1994

Effect of peptidases at the blood brain barrier on the permeability of enkephalin.

The blood brain barrier (BBB) presents an enzymatic barrier to the passage of peptides, from blood to brain. The studies presented here used a well established in vitro model of the BBB to measure the presence of peptidases and the permeability of two opioid peptides. The in vitro BBB model consisted of confluent monolayers of bovine brain microvessel endothelial cells (BMECs). Enkephalin metabolizing enzymes, total aminopeptidase, aminopeptidase M (APM), angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) activities were measured in BMEC monolayers. The effect of specific inhibitors of APM, ACE and NEP on the permeability of [Met5]enkephalin (Met-Enk) and a conformationally constrained and enzymatically stable analog, DPDPE, also was determined. High levels of membrane-associated enzyme activity were measured for total aminopeptidase, APM and ACE. Interestingly, the permeability coefficient of Met-Enk was increased 4-fold in the presence of specific inhibitors of APM and ACE. Low levels of NEP activity were measured in BMEC monolayers and inhibition of NEP had no effect on Met-Enk permeability. The permeability coefficient for DPDPE was not increased with enzyme inhibitors but was 4-fold greater than Met-Enk alone. In the presence of APM or ACE inhibitors, there was no difference in the permeability of DPDPE and Met-Enk. These experiments demonstrate the presence of specific peptidases in BMECs and that the presence of inhibitors to Met-Enk inactivating peptidases significantly increased permeability of this biologically active peptide.

Amino Acid Sequence↗
PubMed1994

Increased albumin permeability in vitro following alterations of glomerular charge is mediated by the cells of the filtration barrier.

The charge-related determinants of albumin permeability have been the subject of much controversy. We have examined the permeability of either isolated glomerular basement membrane (GBM) or intact glomeruli in an in vitro filtration system to determine the effects of biochemical modifications selected to alter the molecules commonly implicated in restricting the glomerular permeability of anionic macromolecules such as albumin. Treatment of isolated GBM with heparatinase to remove heparan sulfate proteoglycan anionic side chains or protamine to effect charge neutralization had no effect on the albumin sieving coefficient. Protamine decreased hydraulic conductivity. pH titration to encompass the isoelectric point of GBM and albumin resulted in a modest increment in albumin permeability. In contrast, when intact glomeruli were treated with either heparatinase or protamine, albumin permeability doubled and protamine treatment of glomeruli resulted in an even greater augmentation of albumin permeability. These results suggest that, to the extent that in vitro GBM is similar to in vivo GBM, the restriction in albumin permeability due to glomerular charge requires the presence of glomerular cells.

Albumins↗
PubMed1976

The role of altered intestinal permeability in the pathogenesis of salmonella diarrhea in the rhesus monkey.

The pathogenesis of Salmonella diarrhea is unclear. Bacterial invasion of the ileal and colonic mucosa resulting in an intense ileocolitis regularly occurs in concert with secretion of water and sodium in jejunum, ileum, and colon. To examine the role of altered permeability in Salmonella diarrhea we studied intestinal histology, water and electrolyte transport, clearance of intravenously injected [14C]erythritol and [3H]mannitol, and changes in transmural electrical potential difference in normal and Salmonella-infected rhesus monkeys. In normal animals, absorption of water and sodium occurred in jejunum, ileum, and colon and a gradient of diminishing permeability from jejunum to ileum to colon for both erythritol and mannitol was observed. Permeability as measured by determining permeability coefficients was not increased by Salmonella infection and in fact was significantly reduced for erythritol in the jejunum of infected animals. Perfusion with hypertonic erythritol and mannitol produced the same streaming potentials (deltaPD) in control and infected animals, indicating no differences in transmucosal permeability. As a positive control, perfusion with 25 mM ethylenediaminetetraacetic acid in normal animals increased permeability, resulting in increased plasma-to-lumen isotope flux and no deltaPD in response to hypertonic perfusates. These data show that despite severe alterations in intestinal histology, transmucosal permeability remains unchanged and thus is not a contributing factor in Salmonella diarrhea.

Animals↗