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PubMed1987

The effect of hypertension on glomerular structures and capillary permeability in passive Heymann glomerulonephritis.

In glomerulonephritic and normal kidneys hypertension has been shown to increase the urinary protein excretion and the thickness of the glomerular basement membrane and to reduce the glomerular filtration rate. We have studied the effect of desoxycorticosterone acetate (DOCA)-salt hypertension on the glomerular anatomy and function in normal control rats and rats with passive Heymann nephritis. Standard methods for measurements of glomerular filtration rate and urinary protein excretion were used and the results were correlated to morphometrical measurements in randomly selected glomeruli in all groups. In control rats, DOCA-salt hypertension increased the kidney weight (P less than 0.001), the glomerular volume (P less than 0.05), and the surface of peripheral glomerular basement membrane (P less than 0.01). The thickness of peripheral glomerular basement membrane and the length of glomerulary capillaries were not affected. In glomerulonephritic rats, DOCA-salt hypertension did not change the kidney weight and glomerular capillary diameter. The thickness of the peripheral basement membrane increased (P less than 0.05), while the length of glomerular capillaries and the surface of peripheral basement membrane were reduced (P less than 0.05). Glomerular filtration rate per unit peripheral basement membrane was not significantly different among the groups while protein excretion per unit peripheral basement membrane increased significantly both in the hypertensive and in the glomerulonephritic groups. The estimated hydraulic conductivity of the glomerular capillaries was reduced both in rats with DOCA-salt hypertension and glomerulonephritic rats with and without DOCA-salt hypertension. In conclusion, DOCA-salt hypertension seems to decrease hydraulic conductivity and increase protein excretion both in normal and in glomerulonephritic kidneys although the effect on glomerular morphology is different.

Animals↗
PubMed1994

Measurement of capillary permeability from the Gd enhancement curve: a comparison of bolus and constant infusion injection methods.

Dynamic imaging of Gd-DTPA uptake has been used by several groups to characterise the permeability of blood-brain barrier and blood-retina barrier lesions, using both bolus and constant infusion rate injections. However, no consensus on which injection protocol is most efficient has been reached. To address this problem, we extend our Simplified Early Enhancement (SEE) theory, applicable to retinal lesions, to cover infusion injections, and demonstrate its application to published data. The two injection methods are compared using computer simulation. We find that, first, an infusion cannot produce a constant plasma concentration in an acceptable time (although a hybrid injection, consisting of a combined bolus and infusion, is able to do this). Second, at any given time after the start of injection, a bolus achieves a higher tissue concentration, and hence enhancement, than does the same dose given as an infusion. Conversely, a bolus achieves any given tissue concentration in a shorter time than the same dose given as an infusion. Consequently, a bolus uses a smaller dose to achieve a given enhancement at a particular time. Third, if renal function is reduced, the error in calculating the permeability from a particular value of enhancement is lower for the bolus than for the infusion. And last, the SEE method is more accurate for a bolus than for an infusion. We conclude that a bolus is always more efficient than an infusion, as well as being easier to administer, and should always be used in preference to an infusion.

Capillary Permeability↗
PubMed1979

Nonhemodynamic effects of histamine on gracilis muscle capillary permeability.

The effects of histamine were studied in the maximally vasodilated gracilis muscle. Dog gracilis muscles were isolated in a plethysmograph and perfused at constant inflow pressure (102 +/- 2 mm Hg). Maximal vasodilation was produced with constant infusion of papaverine (0.2 mg/ml). Constant infusion of blood labeled with albumin-131l or red blood cells (RBC)-51Cr was made throughout the duration of the experiment. Tissue radioactivity and tissue volume changes were continuously measured. Papaverine did not increase transcapillary movement of protein, Histamine (5 microgram/kg/min) was added to the blood and 10 to 15 min later the dose level was increased to 60 microgram/kg/min. Since the vasculature was maximally dilated, changes in tissue radioactivity and tissue volume would be due to transcapillary movement rather than to vascular volume effects. The low dose of histamine significantly steepened the slopes of tissue volume and tissue albumin-s131l increase. The highest dose of histamine significantly further increased these rates. The tissue red cells-51Cr slope was not significantly increased with either dose of histamine. The capillary filtration coefficient was significantly increased above the papaverine vasodilation value by the histamine. The data would support increased transcapillary movement of proteins by other than hemodynamic mechanisms.

Animals↗
PubMed1979

Capillary permeability in cat choroid, studied with the single injection technique (II).

Transcapillary movements of 22Na, 51Cr-EDTA and 125I-myoglobin were studied in the cat choroid by means of the single injection technique, using labelled albumin as the reference tracer. By an external shunting of blood, recirculation of tracer was delayed and complete venous outflow curves became available for analysis. The initial extractions observed were 0.66, 0.35 and 0.08 respectively. The extractions decreased with time. Within 20--25 s the extracted fractions of the tracers had almost completely returned to the blood. The results indicate high permeability coefficients and small extravascular volumes of distribution. The retinal pigment epithelium seems to have a very low permeability to all three substances. Extraction of tritiated water at 20--25 s was about 0.30 probably due to rapid penetration of labelled water into the retina. Evidence for a stereo-specific transport system for glucose in the retinal pigment epithelium was found in experiments with labelled D-glucose and 3-O-methyl-D-glucose. The total amount of glucose delivered by the choroid was calculated from measurements of the a-v differences for unlabelled glucose.

Animals↗
PubMed1988

Neutrophil degranulation and increased pulmonary capillary permeability following oesophagectomy: a model of early lung injury in man.

In nine subjects undergoing oesophagectomy a transient but significant increase in pulmonary vascular permeability to transferrin was detected in both lungs 8 h after surgery. It coincided with a significant increase in plasma lactoferrin, evidence of intravascular and intra-alveolar neutrophil elastase release and with arterial hypoxaemia. The postoperative state in these patients had intravascular and pulmonary features often associated with the adult respiratory distress syndrome, and might be a useful model for the study of the early inflammatory events underlying lung injury in man.

Aged↗
PubMed1975

[Effects of colchicine and of emetine on capillary permeability].

Colchicine and emetine administered locally in the hind paw of the rats increased markedly the capillar permeability. The action may be strongly inhibited by methysergide (0.2 mug). Mepyramine (0.5 mug) is not so active and indomethacine (1 mg/kg per os), even less. As some prostaglandines release serotonine and histamine (8) it is possible that some liberation of these mediators may be attribuable to a previous release of prostaglandines, but the experiments suggest also the possibility of a direct and concomitant release of those two mediators by the alkaloids assayed.

Animals↗
PubMed1990

The use of caesium iodide mini scintillation counters for dual isotope pulmonary capillary permeability studies.

A commercially available system of caesium iodide crystal mini-detectors (Oakfield Instruments, Oxon, UK) was modified so that it was suitable for dual isotopic measurement of the plasma protein accumulation index (PPA)- a measure of pulmonary endothelial permeability. Using this modified system the mean PPA x 10(-3) min-1 +/- (S.E.M.) recorded in 11 normal subjects (22 lungs) was 0.18 (0.08) and in 6 patients (9 lungs) with the adult respiratory distress syndrome was 2.88 (0.63) (P less than 0.02). These values for PPA concur with those found by other groups using larger sodium iodide detectors. We conclude that with simple modification caesium iodide mini-detectors may be used successfully for the measurement of PPA in the intensive care setting.

Capillary Permeability↗
PubMed1984

[Hypovolemic shock caused by an increase in capillary permeability after cesarean section].

A 24 year old woman was delivered by caesarean section after an uncomplicated full-term pregnancy. Non-specific prodromes appeared 48 h later, with development of a severe shock. After confirmation of hypovolaemia, attention was focused on the abnormal haematological findings (a sharp drop in serum proteins with a rise in haematocrit) which suggested major leakage of plasma. Treatment based on infusions of plasma and albumin failed, and the patient died in a state of anasarca and pulmonary oedema with normal wedge pressure. 18 similar cases have already been published, six of which were in obstetric or surgical patients. After analysing the prodromes and its onset, its pathophysiological mechanisms and treatment are discussed.

Adult↗
PubMed1983

Mild hypothyroidism and oedema: evidence for increased capillary permeability to protein.

Nine female patients with normal serum total thyroxine (T4) and triiodothyronine (T3) but elevated thyroid stimulating hormone (TSH) levels were studied. Six patients had generalised oedema associated with maximal diurnal weight gains in excess of 1.4 kg. Under conditions of forced water diuresis, before and during physiological replacement of 1-thyroxine, the supine transcapillary escape rate of albumin (TERA) was measured, while the venous colloid osmotic pressure (COP), packed cell volume (PCV) and urinary excretion of water and electrolytes were studied in both the supine and upright positions. The TERA, diurnal weight gain and orthostatic increase in COP fell significantly with treatment. In the six patients with oedema and excessive diurnal weight gains, the retention of salt and water on tilting was reduced with thyroxine treatment. In female patients we consider generalised oedema associated with excessive diurnal weight gain, to be a common and early symptom of hypothyroidism, meriting thyroxine replacement therapy.

Adult↗
PubMed1989

[Ultrastructure of capillary permeability in malignant lymphoma].

The ultrastructure of the blood vessels of primary central nervous system malignant lymphoma was studied and compared with those in glial, non-glial and metastatic brain tumors. Five surgical specimens were studied by conventional ultrathin section and freeze-fracture replica techniques. Tumor vessels of various sizes were found. The luminal surfaces of the tumor vessels were irregular and the basal lamina had multiple-layer structure. The perivascular spaces were enlarged and infiltrated with tumor cells. The endothelium had marked infoldings, increased pinocytotic vesicles and fenestrations. The intercellular junctions were short but no obvious opening was seen. On the replica specimen pinocytotic vesicles were calculated on an average of 28 per microns2. The essential features of the blood vessels in primary central nervous system malignant lymphoma were the fenestrated vessels. They resembled the blood vessels found in non-glial and metastatic brain tumors, but were distinctly different from those seen in glial tumors with non-fenestrated vessels.

Adult↗
PubMed1980

Changes in gastric mucosal morphology, capillary permeability and blood flow during the first 3 days of acute gastritis in cats.

In the present investigation gastric morphology, blood flow, vascular permeability and water content were studied in cat stomachs with acetic acid-induced gastritis at different time intervals up to 3 days after induction of gastritis. The morphological changes including mucosal erosions, edema and hemorrhage showed normalization within 3 days. The mucosa and muscularis blood flow remained essentially unchanged compared with pre-gastritis values and with the control group. Gastritis was associated with leakage of circulating albumin into the stomach wall most pronounced 4 h after the induction of gastritis. The water content was high at 4 and 24 h after induction of gastritis with almost normalization at 3 days. The morphologaical characteristics of our model are very similar to those observed in man. Leakage of circulating albumin into the gastric wall seems to be the best parameter for quantifaication of the inflammatory changes found in acute gastritis, while blood flow seems to be a less important parameter.

Acute Disease↗
PubMed1987

Effect of bumetanide in capillary permeability pulmonary oedema.

UNLABELLED: To determine if bumetanide, like furosemide, improves shunt through pulmonary vasoactivity, 20 dogs with unilobar oleic acid pulmonary oedema were studied. Fractional perfusion and intrapulmonary shunt of the oedematous lobe were measured at: baseline, 1 1/2 hours after oleic acid infusion, 15 minutes later after either 0.1 mg X kg-1 of bumetanide in ten dogs (Bumetanide Group) or without bumetanide in ten dogs (Control Group), and 2 1/2 hours after the oleic acid, the bumetanide being administered immediately after the 1 1/2 hours post-oleic acid measurements. Lobar shunts for the Bumetanide Group were: 9.3 +/- 4.0, 54.3 +/- 13.6, 54.7 +/- 13.6, 38.6 +/- 12.0 per cent and for CONTROLS: 8.7 +/- 1.6, 45.1 +/- 8.8, 48.3 +/- 7.8, 70.4 +/- 6.2 per cent. Fractional perfusions of the oedematous lobe were: 29.9 +/- 1, 14.7 +/- 1.1, 14.6 +/- 0.7, 19.3 +/- 1.9 per cent in the Bumetanide Group and 28.6 +/- 2.1, 14.2 +/- 1.1, 14.2 +/- 1.5, and 9.9 +/- 1.1 per cent in CONTROLS. Oedema (wet to body weight ratio) was less (p less than 0.05) in the contralateral lobe (2.5 +/- 0.2 vs. 2.9 +/- 0.3) and the oedematous lobe (4.7 +/- 0.4 vs 6.0 +/- 0.5) after bumetanide-induced diuresis. We conclude that bumetanide decreases shunt by decreasing oedema and not through pulmonary vasoactivity.

Animals↗
PubMed1994

Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules.

Caveolae or noncoated plasmalemmal vesicles found in a variety of cells have been implicated in a number of important cellular functions including endocytosis, transcytosis, and potocytosis. Their function in transport across endothelium has been especially controversial, at least in part because there has not been any way to selectively inhibit this putative pathway. We now show that the ability of sterol binding agents such as filipin to disassemble endothelial noncoated but not coated plasmalemmal vesicles selectively inhibits caveolae-mediated intracellular and transcellular transport of select macromolecules in endothelium. Filipin significantly reduces the transcellular transport of insulin and albumin across cultured endothelial cell monolayers. Rat lung microvascular permeability to albumin in situ is significantly decreased after filipin perfusion. Conversely, paracellular transport of the small solute inulin is not inhibited in vitro or in situ. In addition, we show that caveolae mediate the scavenger endocytosis of conformationally modified albumins for delivery to endosomes and lysosomes for degradation. This intracellular transport is inhibited by filipin both in vitro and in situ. Other sterol binding agents including nystatin and digitonin also inhibit this degradative process. Conversely, the endocytosis and degradation of activated alpha 2-macroglobulin, a known ligand of the clathrin-dependent pathway, is not affected. Interestingly, filipin appears to inhibit insulin uptake by endothelium for transcytosis, a caveolae-mediated process, but not endocytosis for degradation, apparently mediated by the clathrin-coated pathway. Such selective inhibition of caveolae not only provides critical evidence for the role of caveolae in the intracellular and transcellular transport of select macromolecules in endothelium but also may be useful for distinguishing transport mediated by coated versus noncoated vesicles.

Animals↗
PubMed1990

Capillary permeability: atrial peptide action is independent of "protein effect".

Perfusion of exchange microvessels with the vasoactive hormone, atrial natriuretic peptide (AP), acutely and reversibly elevates hydraulic conductivity (Lp) by mechanisms that are, as yet, unknown. This, the first of two studies to characterize AP responses when perfusate composition was altered, specifically focuses on the action of AP when perfusate albumin was lowered to change the transcapillary barrier properties for water by passive mechanisms (protein effect). Perfusion of frog (Rana pipiens) mesenteric microvessels with 1 nM AP in 10 mg/ml bovine serum albumin (BSA) elevated Lp by a median 2.1-fold (range 1.2-2.7, n = 13) from control levels (10 mg/ml BSA). Reduction of perfusate albumin from 10 to 1 mg/ml elicited a small rise in Lp (1.8-fold, n = 10); Lp rose a further 2.1-fold (n = 6) when 1 nM AP was added to 1 mg/ml BSA. Likewise, protein-free perfusion elevated Lp from a median 2.2 to 5.1 X 10(-7) cm.s-1.cmH2O-1 (n = 11); 1 nM AP in protein-free perfusate elevated Lp a further 2.1-fold (n = 8). Thus, regardless of protein content, the response to the peptide was a consistent, twofold increase in exchange vessel Lp (n = 27). These data are consistent with the suggestion that the AP-activated rise in Lp (twofold) occurs via an increase in the effective area of the transcapillary pathway for water without influencing the selectivity properties of the paracellular, albumin-sensitive portion of the barrier.

Animals↗
PubMedDate not supplied

Effect of volume expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats.

General and splanchnic hemodynamics (radioactive microspheres), renal function, spontaneous and histamine-mediated vasopermeability and albumin distribution space were studied in conscious control and nonascitic cirrhotic rats, before and after a moderate and sustained saline infusion (3% of body weight per 30 min + repletion of urinary losses). In basal conditions, cirrhotic rats showed lower fractional sodium excretion than did control rats (0.09 +/- 0.01 vs. 0.15 +/- 0.01%, p less than 0.005). In addition, cirrhotic animals showed higher cardiac output (161.4 +/- 12.8 ml per min) and lower total peripheral resistance (0.63 +/- 0.05 mm Hg . min per ml) and mean arterial pressure (102.9 +/- 3.9 mm Hg) than did control rats (cardiac output: 89.0 +/- 7.6; total peripheral resistance: 1.31 +/- 0.11; mean arterial pressure: 117.5 +/- 5.11; p less than 0.005). No differences in portal-systemic shunt rate or vasopermeability between both groups were observed. After saline infusion, fractional sodium excretion increased to 4.31 +/- 0.16% in controls but only 2.11 +/- 0.02% in cirrhotic animals. In this group, cardiac output decreased by 49.6 +/- 5.1% whereas mean arterial pressure and total peripheral resistance increased by 7.1 +/- 0.6 and 112 +/- 10%, respectively. In control rats, no significant hemodynamic changes were observed. Blood gases did not change after expansion in any group. Saline infusion induced an increase in histamine-mediated vasopermeability in cirrhotic rats but not in control rats. Also albumin distribution space increased more in cirrhotic than in control animals. Heart weight was higher in cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

[Ultrastructure of capillary permeability in human brain tumors. 3: Mechanisms of contrast enhancement in non-glial tumors].

In order to elucidate mechanisms of contrast enhancement on computed tomography observed in non-glial tumors, tumors vessels were studied with conventional ultrathin section and freeze-fracture replica techniques. The materials were obtained from surgically removed specimens in 19 cases of tumors (6 of meningioma, 6 of hemangioblastoma, 5 of pituitary adenoma, and 2 of acoustic neurinoma). The following results were obtained. The common findings of these non-glial tumor vessels in ultrathin preparations were surface infoldings, increased pinocytotic vesticles and many fenestrations of endothelial cells, irregularity of basal laminae, and enlarged perivascular spaces. In freeze-fracture replicas of vascular endothelium, pinocytotic vesicles and fenestrations were 22 and 26 per micron2 on the average respectively. Tight junctions between endothelial cells were composed of one or two strands which appeared to be a discontinuous array of particles. As for the each non-glial tumor, menigiomas showed endothelial thickness and finger-like projections, variable lengths of tight junctions and marked enlargement of perivascular space which contained many collagen fibrils. Thinning of endothelium and many fenestrations were observed in hemangioblastomas, pituitary adenomas, and acoustic neurinomas. Fenestrations were most frequently observed in pituitary adenomas. The results indicate that extravasation of contrast material through fenestrations has an important role in marked contrast enhancement of non-glial tumors, in addition to the osmotic opening of tight junctions by contrast material. The irregular basal lamina and large perivascular space may also contribute to an increased extravasation of contrast material.

Adenoma↗
PubMed2006

Nature of glomerular capillary permeability changes following acute renal ischemia-reperfusion injury in rats.

This study was performed to evaluate the alterations of glomerular filtration barrier characteristics following acute renal ischemia-reperfusion (I/R). Ischemia was induced in anesthetized rats by unilateral renal artery occlusion for either 20 or 60 min, followed by reperfusion during 20 or 60 min, respectively, with the contralateral kidney serving as control. Sieving coefficients (theta) were obtained by analyzing Ficoll [mol.radius (a(e)) 13-85 A] in urine and plasma after 20 and 60 min I/R. Furthermore, theta for human serum albumin (HSA) was estimated using a tissue uptake technique after 20 and 60 min of I/R, while clearance of HSA compared with that for neutralized HSA (nHSA) was assessed after 20 min of I/R only. Glomerular filtration rate (GFR) was measured by [51Cr]EDTA and inulin. I/R reduced GFR and increased theta for Ficoll molecules of a(e) >55 A and theta for albumin. theta for Ficoll vs. a(e), analysed using a two-pore model, demonstrated that, despite increases in theta, the large-pore fractional ultrafiltration coefficient (alpha(L)) was unchanged after 20 min of I/R, owing to the decline in GFR, but increased after 60 min of I/R. However, the apparent alpha(L) for albumin increased already after 20 min of I/R (P < 0.005) and the nHSA/HSA clearance ratio was slightly reduced, possibly reflecting a diminished negative charge barrier. In conclusion, after 20 min of I/R, indications of a reduced charge selectivity were noted, while after 60 min of I/R, there was mainly a reduction in size selectivity, compatible with an increased formation of large pores.

Acute Disease↗
PubMed1992

Quantitation of specific binding of orosomucoid to cultured microvascular endothelium: role in capillary permeability.

Orosomucoid (also known as alpha 1-acid glycoprotein) is a highly sialylated, polyanionic serum glycoprotein. Its presence in vascular perfusates alters microvascular permeability, presumably by binding to the endothelial glycocalyx, but the rest of its functions remains unknown. In this study, we assess the binding of bovine serum orosomucoid (BSO) to the surface of bovine pulmonary microvascular endothelial cells (BLMVEC) in culture at 4 degrees C. The binding of radioiodinated BSO (125I-BSO) reached equilibrium after 10 min of incubation, was not calcium dependent, and was reversible by greater than 80% in 30 min. The binding of 125I-BSO was competed with unlabeled BSO but not by transferrin, immunoglobulin, gelatin, ovalbumin, mannan, fucoidan, mucin, or asialomucin. In addition, binding was not affected by the presence of galactose, glucose, fucose, mannose, N-acetyl-D-galactosamine, or N-acetyl-D-glucosamine. This binding behavior is not consistent with carbohydrate recognition by lectin-like molecules such as the asialoglycoprotein receptor. Scatchard analysis of the BSO binding to BLMVEC produced a concave-upward shaped curve, which revealed a higher affinity binding component with an apparent equilibrium affinity constant (Kd) of 8.6 nM and a maximum receptor number of 40,000/cell and revealed a moderate affinity component with a Kd of 9.1 microM with a maximum binding of 10(7) binding sites per cell. Other blood vessel-associated cells clearly bound less BSO with a lower binding affinity than the BLMVEC monolayers. From the binding data, we estimated the total increase in the negative charge of the glycocalyx with orosomucoid binding to be approximately 17 meq/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗