Bradykinin (BK) in an asanguinous salt solution was perfused through intact rat liver. The perfusate was delivered through the portal vein and was collected from the inferior vena cava. BK concentrations varied from 0.0030 to 38.0 microm. The liver had a large capacity to degrade BK and the system did ...

We have tested the hypothesis that the leak of protons across the mitochondrial inner membrane (proton leak) is a significant contributor to standard metabolic rate (SMR). We found that proton leak accounts for around one-half of the resting respiration rate of perfused rat skeletal muscle. Proton leak is known to ...

Changes in blood flow induced by the beta-adrenoceptor agonist isoproterenol (Iso) and a stable analogue of the major metabolite of arachidonic acid in adipose tissue, carbaprostacyclin (cPGI2), have been studied in rat periepididymal fat pad with in situ microdialysis measuring the distribution ratio of 0.2% ethanol in the dialysate (outflow) ...

BACKGROUND & AIMS: Capillarization of the sinusoids in cirrhosis is proposed to reduce oxygen availability to the hepatocyte, resulting in the patterns of altered drug metabolism observed in cirrhosis. If this were true, drug metabolism in cirrhotic livers would be expected to be more sensitive to reduced oxygen delivery than ...

Acyl glucuronides are reactive electrophilic metabolites and in vivo are readily hydrolyzed, undergo intramolecular rearrangement, and bind covalently to proteins. The isolated perfused liver preparation, using male Sprague-Dawley rats, was used to examine the hepatic disposition of the fibrate hypolipidemic agent gemfibrozil and its acyl glucuronide metabolite, 1-O-gemfibrozil-beta-D-glucuronide. Using a ...

1. The disposition of tacrine 1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA, Cognex), was studied using livers obtained from control, phenobarbital (PB), isosafrole (ISO), and 3-methycholanthrene (3-MC) treated rats. 2. Pretreatment of rats with PB, ISO, and 3-MC reduced AUC(10-120 min) of THA in liver perfusates by 28, 32, and 86% respectively. 3. ...

The distribution of control over the resting respiration rate (and other variables) was assessed in perfused rat skeletal muscle. The results indicate that the general pattern of control in resting muscle is similar to that seen in isolated rat liver cells (Brown et al. (1990) Biochem. J. 192, 355-362). Control ...

1. Isolated rat filtering kidneys were perfused with Ringer bicarbonate solutions containing either trifluoperazine (TFP, 50 microM) or verapamil (VER, 100 microM) to prevent tissue dysfunctions observed during perfusion. 2. Water, sodium and chloride kidney contents diminished under both treatments as compared with control preparations, and potassium content increased. 3. ...

Individual ducts from the initial zone of the efferent ducts of the rat were microperfused in vivo using a double cannulation procedure, which allowed the recovery of perfused fluids for analysis and determination of the rate of fluid reabsorption from the perfused duct. The ducts were perfused at rates from ...

The dose-dependent elimination of formate was investigated in the rat using both in vitro and in vivo systems. The in situ perfused liver was used to define the kinetics of hepatic metabolism and obtain initial in vitro estimates of the hepatic metabolism kinetic parameters. Formate was eliminated from the perfused ...

To investigate the carnitine deficiency induced by pivalate, rats had free access to drinking water with or without pivalate. Consumption of 20 mmol/L pivalate for 1 wk decreased the levels of both free and total carnitine in plasma to approximately 20% of levels before treatment. After 4 wk, the concentrations ...

Endosomes and lysosomes are acidified by an electrogenic proton pump in parallel with a chloride conductance and in kidney both of these may be regulated by cAMP. In vitro exposure of isolated rat liver endosomes to cAMP, PKA and GTP-gamma S stimulated acidification of "early" endosomes with or without C1-, ...

BACKGROUND/AIMS: The aim of the study presented here was to evaluate the basal and stimulated phagocytic activities and the metabolite production of isolated perfused livers, and also the phagocytic capacity of cultured Kupffer cells from rats with macronodular cirrhosis. METHODS: Rats were made cirrhotic by oral administration of thioacetamide. The ...

To test whether high-density lipoproteins (HDL) could aid in the removal in vivo of potentially atherogenic oxidized lipids, we perfused rat liver in situ with buffer supplemented with isolated human HDL containing small amounts of cholesteryl linoleate hydro(pero)xides [CH18:2-O(O)H]. Perfusion resulted in the rapid removal of Ch18:2-O(O)H from HDL with ...

The effects of progesterone (P) on serotonin (5HT) overflow in the ventromedial hypothalamus (VMH), preoptic area (POA) and midbrain central grey (MCG) were studied using in vivo microdialysis. Ovariectomized rats, pretreated with 5 micrograms estradiol, were anesthetized with chloral hydrate and stereotaxically implanted with dialysis probes directed towards one of ...

Satisfactory purification of rodent monocytes in suspension has not been achieved up to now because in rats and mice these cells occur as a minor population of peripheral blood leukocytes overlapping with lymphocytes in size and density. We describe a two-step procedure for the isolation of monocytes from rat blood ...

In this study, the possible role of the hepatic microcirculation in phalloidin-induced cholestasis and hepatotoxicity was examined in isolated perfused rat livers (IPRL). Administration of a phalloidin bolus (1 mg/kg body weight) through the portal vein induced an immediate reduction of bile flow. In 16.9 minutes, bile flow was 50% ...

The metabolism of diacetyl (2,3-butanedione), acetoin (3-hydroxy-2-butanone), and 2,3-butanediol, which are metabolites of acetaldehyde was quantitatively investigated using rat liver homogenate, liver perfusion, and in vivo experiments. Diacetyl and acetoin were reduced to 2,3-butanediol in these experiments, but acetoin and 2,3-butanediol were scarcely oxidized to diacetyl, indicating that the reduction ...

The completely hepatectomized rat has frequently been used as a model to study changes in the economy of norepinephrine (NE) and dopamine (DA) in hepatic coma. Hypothermia characteristically develops in hepatectomized rats and also occurs in patients in hepatic coma and is associated with improved survival in both. The aims ...

Livers from male Sprague-Dawley rats were perfused with heparinised, unmodified isogeneic rat blood (n = 6) or xenogeneic human blood. The microcirculation of these livers, as the primary manifestation of hyperacute xenogeneic rejection, was directly observed and quantified by using fluorescence videomicroscopy. Bile flow and enzyme release of the isogeneic ...

1. The actions of piroxicam, a nonsteroidal and noncarboxylic anti-inflammatory drug, on the metabolism of the isolated perfused rat liver were investigated. The main purpose was to verify if piroxicam is also active on glycogenolysis and energy metabolism, as demonstrated for several carboxylic nonsteroidal anti-inflammatories. 2. Piroxicam increased oxygen consumption ...

We studied the incorporation of 14C-formate into uric acid and allantoin in different organs (liver, lung, kidney, spleen), isolated hepatocytes, perfused liver and urine of the rat. Allantoin had a higher specific radioactivity than uric acid after 14C-formate load in the liver in vivo. This was found to be a ...

The isolated perfused rat lung (IPL) was perfused with 60 ml of recirculating Krebs-Ringer solution containing 150 micrograms of 1-nitropyrene (1-NP) for 1 h. The 1-NP was administered to the IPL by the intratracheal or intravascular route. At specific time points after 1-NP administration, perfusate samples were removed from the ...

The reabsorption of 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) by the renal proximal tubule has an important role in the maintenance of plasma folate concentrations. However, the mechanism by which this vitamin traverses the renal epithelium remains to be determined. Studies in cultured cells have suggested that the folate receptor in association with ...

Previous designs of isolated rat liver perfusion circuits used for toxicological investigations are often expensive, cumbersome, or traumatic in relation to hepatic biocompatibility following extended perfusion times. A new, miniaturized circuit that incorporates a novel design of organ bath, to maintain a buoyant preparation, and a high-efficiency miniaturized membrane tubing ...

The interaction of 125I-radiolabeled immunoglobulin G (IgG), F(ab')2, and Fab fragments with different modes of production (polyclonal or monoclonal), belonging to different subclasses (IgG1 and IgGT) and derived from different sources (mouse, rat, and horse) with liver, was investigated by using isolated perfused rat liver and isolated rat hepatic parenchymal ...

The distribution kinetics of 5-ethyl barbituric acid (EBA) has been examined in the rat liver. The isolated in situ liver (n = 4) was perfused at a constant rate (15.1 +/- 0.2 ml/min, mean +/- S.D.) with protein-free Krebs bicarbonate medium in a single-pass mode. [14C]Sucrose (extracellular reference) and [14C]EBA ...

Experimental perfusions of isolated rat kidneys were performed with flow rates adjusted to produce comparable glomerular filtration rates (GFR) in control and experimental groups. The experimental perfusate, consisting of Krebs-Ringer bicarbonate (KRB) containing 3.5% (uncrosslinked) stroma-free hemoglobin (SFH) plus 3.5% of the perfluorochemical (PFC) Fluosol-DA, was found to produce only ...

1. The experiments described in this paper aimed to determine whether the gaps which develop in microvascular endothelium in association with increases in permeability are located in the intercellular clefts or are openings passing through the endothelial cells. 2. Hydraulic permeability (Lp) was estimated in frog mesenteric capillaries and single ...

1. Hepatic removal and metabolism as well as biliary excretion of noradrenaline were studied. Rat livers were perfused in situ for 60 min with Krebs-Henseleit buffer at 37 degrees C containing 2 nM [3H]-(-)-noradrenaline. [3H]-noradrenaline and its [3H]-metabolites were determined in liver, venous effluent and bile. 2. Removal of [3H]-noradrenaline ...

The present study was undertaken to investigate the in vitro and in vivo pharmacological profile of the novel, nonpeptide neuropeptide Y (NPY) Y1-selective antagonist, BIBP 3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-am ide], and a recently described peptidic structure [Ile-Glu-Pro-Orn-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic (2,4'), (2',4)-diamide]. BIBP 3226 antagonized the NPY Y1 receptor-mediated decrease in the twitch response ...

The pathophysiology of lethal intoxication by botulinolysin (Blyn) was studied using anesthetized rats and isolated rat organs. Intravenous injection of 10,000 and 1000 hemolytic units (HU) of Blyn killed rats rapidly while 100 HU of the toxin did not. Congestion and edema of lungs were observed at autopsies of the ...

The study of corrosion casts by scanning electron microscope is an established means of investigating three-dimensional microvascular architecture. However, concern has been raised that the volume of the vasculature is affected by the perfusion procedure. Ten rats (group A) were standard perfusion fixed, while 10 rats (group B) were perfused ...

The nasal secretions are the first barrier that nasally administered drugs encounter. Therefore, the characterization of peptide metabolism in the nasal secretions is essential to predict nasal peptide bioavailability. Metabolism of bradykinin was measured in rat and sheep nasal secretions to estimate the extent of degradation of nasally administered peptide ...

The effects of adrenomedullin and calcitonin gene-related peptide (CGRP) were compared in the rat isolated perfused kidney and in the anaesthetised rat. Adrenomedullin and CGRP both elicited concentration-dependent vasodilator responses from perfused kidneys (adrenomedullin was less potent than CGRP). These responses were blocked by CGRP-(8-37) (1 microM). Adrenomedullin and CGRP ...

Transferrin receptors are present in the plasma membrane of brain endothelial cells but it is unclear if these receptors mediate transport of transferrin across the blood-brain barrier (BBB). In the present study, the transport of rat holo-transferrin (rTf) across the BBB in vivo was evaluated in ketamine anesthetized rats (250-300 ...

Lipoprotein lipase has been found to efficiently mediate binding of lipoproteins to cell surfaces and to the low density lipoprotein (LDL) receptor-related protein (LRP) under cell culture conditions (Beisiegel et al. 1991. Proc. Natl. Acad. Sci. USA. 88: 8242-8346). This supports the previously proposed idea that the lipase could have ...

The effect of 17 beta-oestradiol and 3 alpha-hydroxy-5 alpha-pregnane-20-one (allopregnanolone) on the action potentials in the Schaffer collateral pathway was investigated in hippocampus CA1. Slices from male and female guinea-pigs and female rats were used. In the rat three groups were studied: (a) untreated prepubertal rats at day 25 after ...

Feeding rats a low-protein (8%) diet (LPD) for 2 wk induces a facilitated urea transporter in rat initial inner medullary collecting ducts (IMCDs). To determine whether this is preceded by an increase in mRNA abundance, we designed degenerate polymerase chain reaction primers to the rabbit facilitated urea transporter (UT2; G. ...

The total ethanolic extract, the phenolic and the alkaloidal fraction of the herb of Chelidonium majus L. (Papaveraceae) were tested for their choleretic activity using the isolated perfused rat liver. The total extract significantly caused chloresis by increasing the bile acid independent flow (BAIF); the observed weak activity of both ...

We investigated whether bile salts (BS) with different hydrophobic-hydrophilic properties interact with ethanol on bile secretion, enzyme (aspartate transaminase [AST], lactate dehydrogenase [LDH]) release in the perfusate, liver ultrastructure, and vesicular exocytosis in the isolated perfused rat liver. Ethanol (0.1 or 1%) promoted a rapid decrease of bile flow and ...

Surfactants are one of the most frequently used adjuvants in oral pharmaceutical preparations, used primarily as solubilizers, stabilizers, emulsifiers, and wetting agents. However, surfactants can disrupt normal membrane structure. In this study, lactate dehydrogenase (LDH) and mucus were evaluated as potential markers of intestinal damage in a single-pass in situ ...

Drug-specific antibody fragments, which can reverse tricyclic antidepressant toxicity in rats, represent a potential clinical treatment for tricyclic antidepressant overdose in humans. To delineate the pharmacokinetic mechanisms, we studied the effects of a high-affinity, drug-specific Fab fragment on desipramine (DMI) disposition in rats and on DMI kinetics in the isolated, ...

Stevioside, the sweet glycoside of Stevia rebaudiana, was perfused in to rat livers in order to see if, according to previous suggestions, the hepatic tissue is able to metabolize this compound. Stevioside, at the concentrations of 0.2 and 0.5 mM, was recirculated during two hours. The concentration of stevioside remained ...

Secretion of bicarbonate has been described for distal nephron epithelium and attributed to apical Cl-/HCO3- exchange in beta-intercalated cells. We investigated the presence of this mechanism in cortical distal tubules by perfusing these segments with acid (pH 6) 10 mM phosphate Ringer. The kinetics of luminal alkalinization was studied in ...

To determine the hepatic fate of alpha-ketoisocaproate (KIC) in cirrhosis, six groups of isolated rat livers were perfused with 0, 0.5, 1 (with or without alpha-[1-14C]KIC), 2, and 5 mM KIC; control livers from healthy rats were studied in parallel under similar conditions. KIC was rapidly removed by the normal ...

Hepatic metabolism of the pyrrolizidine alkaloid monocrotaline results in extrahepatic toxicity caused by the release of metabolites from the liver. We have quantified the release of pyrrolic metabolites into the perfusate and bile of isolated rat livers perfused with monocrotaline over the concentration range of 0.125-1.5 mM. Over a 1-hr ...

Ether lipids show high specific cytotoxicity in vitro on a wide variety of experimental tumors, but only moderate activity in vivo. One reason for this lack of activity in the whole animal might be a high degree of metabolic degradation. We therefore studied the biotransformation of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine ([3H]ET18-OMe) labeled in ...

Nephrotoxicity has represented the major limitation in the use of cyclosporine A (CyA). The structural abnormalities at the level of the proximal tubular cells are necrosis, vacuolisation and lipid droplets, as well as CyA-induced glomerular afferent arteriole constriction and granular juxtaglomerular cell hyperplasia. The mode of action of vasoconstriction is ...

Systemic vascular hyporeactivity to vasoconstrictors has been described in rats following endotoxin administration. Inducible nitric oxide synthase (iNOS) expression is known to occur in the liver in endotoxemia, but consequences of iNOS induction on hepatic hemodynamics are unknown. The reactivity of the hepatic circulation to phenylephrine was tested in perfused ...