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PubMed1995

Analysis of the reactivity of [14C]toluene diisocyanate (TDI) in an isolated, perfused lung model.

An isolated, perfused, guinea pig lung model was used to investigate the molecular events which occur when a 14C-labeled TDI vapor reaches the airways. Exposure concentrations of 0.2 and 0.7 ppm were tested. Perfusate composition included: Krebs Ringer buffer only, as well as buffer containing either guinea pig serum albumin, human serum albumin, or diluted guinea pig plasma. Radioactivity was detected in the perfusate within minutes of exposure, and following a delay, increased linearly. The rate of uptake was dependent on TDI concentration and the composition of the perfusate. Biochemical characterization of the state of the 14C-labeled material in the perfusate was performed. The distribution between low and high molecular weight reaction products was determined by molecular sieve fractionation and varied as a function of perfusate composition but no variability was observed as a function of time during the 45 min of exposure. An increase in nucleophile concentration in the perfusate was associated with both a higher percentage of conjugated products (from 15% with buffer only to 45% with diluted guinea pig plasma) and an increase in the rate of TDX uptake (from 0.5 microns Eq/min with buffer alone to 0.1 micrograms Eq/min with diluted GPSA as perfusate at 0.7 ppm). GC-MS analysis of the samples for free TDA, before and after acid hydrolysis, showed that the low molecular weight product(s), which represented from 55-85% of the circulating radioactivity, was composed of hydrolyzable and non-hydrolyzable conjugates and metabolites with approximately 4% of the label associated with free TDA. Although the distribution between high and low molecular weight species varies, this result is analogous to the findings from in vivo studies and suggests that the isolated, perfused lung (IVPL) system may be a useful tool in investigating the molecular mechanisms of isocyanate-induced disease and metabolic activity of the lung.

Animals↗
PubMed1971

Uptake kinetics and metabolism of 7-3H-dopamine in the isolated perfused rat heart.

1. The isolated, perfused rat heart accumulates dopamine by two distinct uptake mechanisms characterized by different kinetic constrants and different patterns of metabolite production (Uptake 1: Km 0.69 x 10(-6)M and Vmax (1.45 x 10(-9) mol/g)/min; Uptake 2: Km 5.9 x 10(-4)M and Vmax (0.14 x 10(-6) mol/g)/min).2. The metabolic fate of dopamine taken up by the isolated, perfused rat heart depends on the concentration of dopamine in the perfusion medium. At a very low perfusion concentration (0.047 x 10(-10) mol/ml) most of the radioactivity is stored as unchanged dopamine and the main metabolite is noradrenaline. With increasing perfusion concentrations deamination becomes the main metabolic pathway, deaminated metabolites accounting for more than 50% of the total radioactivity after perfusion with 2,614.4 x 10(-10) mol/ml for 16 minutes. The O-methylated, and the O-methylated deaminated metabolites are of minor importance at all perfusion concentrations.3. The resistance to wash out of the dopamine taken up by the isolated, perfused rat heart is dependent on the perfusion concentration used. At a concentration of 66.9 x 10(-10) mol/ml, 50% of the total activity is washed out during an 8 min wash period. Within the same time interval there is no wash out when a perfusion concentration of 0.042 x 10(-10) mol/ml is used.4. It is concluded that the metabolic fate of dopamine taken up at various perfusion concentrations reflects the distribution of dopamine within intra- and extraneuronal compartments in the hearts.

Animals↗
PubMed1978

Evaluation of hypertonic citrate flushing solution for kidney preservation using the isolated perfused rat kidney.

The isolated perfused rat kidney has been used to study the effects of cold ischaemia during ice storage. Tissue adenine nucleotide levels in freeze-clamped kidneys were closely correlated with their function after circulation had been reestablished in the perfusion circuit. The ATP content was depleted to a greater extent than total adenine nucleotide after 8 hr of cold ischaemia but both were considerably diminished after 24 hr. The model was also used to compare four solutions which are available clinically for preliminary flushing of organs in the ice storage preservation technique. The results indicated that for periods of 8 and 24 hr of cold ischaemia, renal function and adenine nucleotide content were significantly better maintained with a solution based on hyperosmolar citrate than with Collins, Sacks, or Perfudex solutions. This study confirmed recent observations of the clinical efficacy of citrate solution, while demonstrating how the isolated perfused rat kidney could be used for rapid screening of modifications in preservation techniques.

Adenine Nucleotides↗
PubMedDate not supplied

Effect of oleic acid on arginine-induced glucagon secretion by the isolated perfused rat pancreas.

The isolated perfused rat pancreas was used to investigate the effect of oleic acid on glucagon secretion in response to 10 mmol/l arginine. In the absence of oleic acid and at 2.5 mmol/l calcium, arginine induced a biphasic glucagon secretion. At lower extracellular calcium concentration (1.0 mmol/l), the second phase of glucagon release was reduced, the first phase being unchanged. In the presence of 1,500 mumol/l oleic acid, the glucagon response to arginine was also biphasic, but second phase release was markedly inhibited, the first phase glucagon release being unchanged. Such an effect was not obtained when oleic acid concentration in the medium was 750 mumol/l. These results demonstrate that high concentrations of oleic acid inhibit glucagon secretion in response to arginine from the isolated perfused rat pancreas and support the concept that circulating free fatty acid levels are involved in the control of glucagon secretion.

Animals↗
PubMed1986

Lung mechanics of the guinea-pig isolated perfused lung.

In the isolated perfused guinea-pig lung, lung resistance (RL) and dynamic compliance (CDYN) as well as flow, pH, PO2 and PCO2 of the perfusate were recorded. The baseline values were stable up to 2.5 h. Mean values (+/- SEM) for RL and CDYN were 0.36 cm H2O ml-1 s-1 +/- 0.04 and 0.27 ml cm-1 H2O +/- 0.02, respectively, which agree with in vivo values reported for unanaesthetized guinea-pigs. The pH was always slightly raised and the PCO2 always lowered in the effluent compared to the inflowing medium (P less than 0.001), indicating that the lung had an operative ventilation. Intravascularly administered acetylcholine, histamine and adenosine caused reproducible dose-dependent bronchoconstrictions recorded as increased RL and decreased CDYN. It is noteworthy that adenosine in this model and in vivo consistently produced bronchoconstriction which is in contrast to findings in other in vitro airway preparations. We conclude that this isolated perfused guinea-pig lung preparation has stable in vivo-like characteristics offering interesting possibilities for combining studies of respiratory effects with, for example, metabolism, pharmacokinetic and vascular reactivity studies.

Acetylcholine↗
PubMed1985

Effects of short-term hypothermic perfusion and cold storage on function of the isolated-perfused dog kidney.

The isolated-perfused dog kidney was used as a model to measure the effects of short-term hypothermic preservation on renal function and metabolism. Kidneys were cold-stored in Collins' solution, hypotonic citrate, or phosphate-buffered sucrose for 4 and 24 hr, or were continuously perfused for 4 and 24 hr with a synthetic perfusate. Following preservation kidneys were perfused with an albumin-containing perfusate at 37 degrees C for 60 min for determination of renal function. The results indicate that many of the effects of short-term preservation on renal function in dog kidneys are similar to results reported for rat and rabbit kidneys. Cold storage for 4 hr resulted in a large decrease in GFR (57%), but only a small decrease in Na reabsorption (from 97 to 87%). Cold storage for 24 hr caused a further decline in renal function (GFR = 95% decrease, Na reabsorption = 49-64%). Results were similar for all cold storage solutions tested. Perfusion for 4 hr was less damaging to renal function than cold storage. The GFR decreased only 14% and urine formation and Na reabsorption were practically normal. After 24 hr of hypothermic perfusion, the GFR was reduced by 79%, urine flow was normal, and Na reabsorption was 78%. There were no obvious biochemical correlates (adenine nucleotides, tissue edema, or electrolyte concentration) with the loss of renal function during short-term preservation. The results suggest that the isolated-perfused dog kidney can be used to test the effects of preservation on renal function, and yields results similar to those obtained using small animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[Limb salvage in osteosarcoma. Significance of preoperative isolation perfusion chemotherapy].

In our Department since 1960 isolation perfusion chemotherapy has been performed as a preoperative procedure combined with surgery in 134 patients with osteosarcoma of the extremity. In this paper, the significance of isolation perfusion chemotherapy was presented. The cumulative 5-year survival rate of 114 perfused patients was 42.7%, while that of 41 non-perfused patients before 1960 was 17.1%. Of the 114 patients 102 underwent amputation and 12 had limb salvage surgery. The cumulative 5-year survival rate of the 9 patients who have received limb salvage surgery since 1978 is 68%. Eleven patients who received preoperative aggressive chemotherapy including isolation perfusion chemotherapy showed a 91% clinical and radiological response to the drug. The tumor was microscopically analyzed and the ratio of necrotic to viable tumor cells was calculated. The degree of tumor necrosis was classified as excellent (greater than or equal to 95%), good (80-94%), fair (50-79%) and poor (less than 50%). The response in 22 patients who received preoperative aggressive chemotherapy using adriamycin, methotrexate and cis-platinum including the use of isolation perfusion was excellent in 41%, good in 36%, fair in 14% and poor in 9%. We believe that preoperative isolation perfusion chemotherapy is an effective procedure for limb salvage surgery.

Adolescent↗
PubMed1986

Effects of stimulation on steroid output and perfusion medium flow rate in the isolated perfused rat adrenal gland in situ.

Using the in-situ, isolated, perfused rat adrenal system, the actions of adrenal stimulants on steroidogenesis and perfusion medium flow rates (under constant perfusion pump conditions) have been studied. In a series of 100 experiments, initial rates of corticosterone output and flow rates were found to be positively correlated, although there was no such relationship between initial rates of aldosterone output and flow rates. Furthermore, in stable perfusion conditions, bolus injections of ACTH increased both flow rate and steroid output in a dose-related manner. In individual experiments there was a clear correlation between corticosterone and flow, but the association between aldosterone secretion rate and flow was less evident. It is possible that this discrepancy arises because of temporal differences in the responses of these two steroids. Flow was also stimulated by dibutyryl cyclic AMP (dbcAMP), with correlations with steroid output similar to ACTH, but the specific zona glomerulosa stimulants angiotensin II amide and potassium ions had, if anything, inhibitory effects on flow, but only at high concentrations. The data suggest that ACTH and dbcAMP evoke specific responses in the adrenal vasculature, resulting in relatively decreased intraglandular vascular resistance. They furthermore suggest that the secretory functions of the inner adrenocortical zones are subject to the additional control of vascular elements in the intact gland.

Adrenal Glands↗
PubMed1985

Effects of lysosomal inhibitors on 125I-insulin and 125I-asialofetuin degradation by the isolated, perfused rat liver and isolated rat hepatocytes.

To further evaluate the role of the lysosomal system in insulin degradation, we have compared the effects of inhibitors of lysosomal function on the degradation of 125I-insulin with 125I-asialofetuin, a lysosomally targeted molecule, by the intact, perfused rat liver and the isolated rat hepatocyte. The inhibitors employed were chloroquine (125 microM), NH4Cl (10 mM), and leupeptin (50 micrograms/ml). In the intact, perfused liver the observed inhibition of 125I-asialofetuin degradation at 30 min was as follows: chloroquine, 38%; NH4Cl, 32%; and leupeptin, 86%. Chloroquine also inhibited 125I-insulin degradation in the intact, perfused liver (29%), but NH4Cl and leupeptin had no effect. Using the isolated hepatocyte, the observed values for inhibition of 125I-asialofetuin at 60 min were: chloroquine, 85%; NH4Cl, 76%; and leupeptin, 81%. Chloroquine produced a 28% inhibition of 125I-insulin degradation, while NH4Cl and leupeptin had no effect. Chloroquine and NH4Cl decreased cell-associated radioactivity when isolated hepatocytes were incubated with 125I-asialofetuin (leupeptin had no effect), whereas chloroquine caused a 107% increase in cell-associated radioactivity when 125I-insulin was added to the incubation media (NH4Cl and leupeptin had no effect). These results indicate that the effects of chloroquine on insulin degradation are an extralysosomal action and that lysosomes appear not to be involved in the physiologic degradation of the insulin molecule.

Ammonium Chloride↗
PubMed1999

Uptake and excretion of sodium taurocholate by the isolated perfused neonatal sheep liver.

We present a model for perfusion of the isolated perfused neonatal sheep liver which allows examination of drug disposition by the intact organ. We studied the disposition of sodium taurocholate (TC) in seven neonatal lambs (ages 2-11 days) and compared the results with earlier data from the perfused fetal sheep liver (Ring, J. A. et al. Biochem. Pharmacol. 1994, 48, 667-674). Measurements of perfusion pressure, oxygen consumption, lactate:pyruvate ratio, bile flow, and liver histology indicated that the preparation was both viable and stable over a 2 h period. [14C]-labeled TC was added to the reservoir by constant infusion (30 micromol/h) and the ductus venosus shunt quantitated by injection of [153Gd]-labeled microspheres. Shunt-corrected hepatic extraction ratio of TC was 0. 56 +/- 0.14 (fetal 0.23 +/- 0.16, p < 0.005) and clearance of TC was 0.92 +/- 0.35 mL/min/g liver (fetal 0.44 +/- 0.23 mL/min/g, p < 0. 01). We conclude that the isolated perfused neonatal sheep liver is a useful experimental model which will facilitate the study of the developmental physiology and pharmacology of the liver. There is considerable maturation of the biliary excretion of TC between the late fetal and early neonatal periods in the lamb.

Aging↗
PubMed1984

Metabolism of leukotrienes B4 and C4 in the isolated perfused rat lung.

Isolated rat lungs perfused with physiological buffer containing leukotriene C4 were found to rapidly metabolize leukotriene C4 to leukotriene C4 sulfoxide, leukotriene D4, and leukotriene E4. Addition of leukotriene C4 to the recirculating perfusion buffer was observed to cause a persistent increase in the pulmonary arterial pressure. Leukotriene C4 instilled into the airway of the perfused lung was also rapidly metabolized to these same products with retention of the products within the lung. In contrast, leukotriene B4 injected into the perfusion fluid was recovered unchanged in the lung effluent. Leukotriene B4 instilled into the airway of the perfused lung was observed to rapidly traverse the alveolar membranes and was recovered intact in the lung effluent. No evidence for formation of the 20-hydroxy or the 20-carboxy metabolites of leukotriene B4 by the isolated perfused rat lung was observed.

Animals↗
PubMed1991

Metabolism of cysteinyl leukotrienes by the isolated perfused rat kidney.

The metabolism of cysteinyl leukotrienes by the isolated perfused rat kidney was investigated. For this purpose LTC4, LTD4 or LTE4 were studied in separate experiments. The isolated perfused rat kidney metabolized all cysteinyl leukotrienes to the final metabolite N-acetyl-LTE4. In the presence of 5% albumin 50% of LTC4 was metabolized to LTD4 (22%), LTE4 (15%) and N-acetyl-LTE4 (13%) within 60 min. Excretion of radioactivity into urine was less than 1%. In contrast, in the absence of albumin, LTC4 was completely metabolized within 45 min to N-acetyl-LTE4, the sole and final metabolite of LTC4 found in the perfusion medium as well as in urine. After 60 min 19% and 42% of total radioactivity were found in the perfusion medium and in urine, respectively. Isolated glomeruli metabolized LTC4 to LTD4 and to LTE4 but not to N-acetyl-LTE4 at a rate comparable to the rate observed by the isolated perfused kidney in the absence of albumin. In contrast to isolated glomeruli isolated tubuli metabolized LTE4 to N-acetyl-LTE4 at a rate comparable to that observed by the isolated perfused kidney in the absence of albumin. The present study shows that the isolated perfused rat kidney metabolizes cysteinyl leukotrienes to the sole and final metabolite N-acetyl-LTE4. In the presence of albumin metabolism is slowed down and excretion of N-acetyl-LTE4 into urine is prevented.

Animals↗
PubMedDate not supplied

Influence of calcium channel inhibitors on the myocardial uptake and retention of technetium 99m N-NOET, a new myocardial perfusion imaging agent: a study on isolated perfused rat hearts.

BACKGROUND: Technetium 99m N-NOET is a new myocardial perfusion imaging agent currently in phase III clinical trials in Europe. In vitro studies on newborn rat cardiomyocytes have shown that calcium inhibitors, such as verapamil or diltiazem, inhibit its cellular uptake by 40%. To determine whether such a specificity exists ex vivo, we studied the effect of verapamil, diltiazem, and nifedipine on the myocardial uptake and retention of Tc-99m N-NOET in isolated perfused rat hearts. METHODS AND RESULTS: After a 15-minute baseline period, rat hearts were perfused with 0.5 micromol/L verapamil (n = 6), 0.75 micromol/L diltiazem (n = 6), or 0.1 micromol/L nifedipine (n = 6) for 10 minutes before the injection of a bolus (40 microCi/250 microL) of the tracer. Control hearts were perfused with either 1.5 mmol/L calcium (same concentration as in the treated groups; n = 7) or 0.75 mmol/L calcium (same contractility as in the treated groups; n = 6). Myocardial activity of Tc-99m N-NOET was monitored for 30 minutes. The functional parameters of the hearts were recorded throughout the experiments. Calcium inhibitors induced a 40% to 55% decrease in maximal first derivative of left ventricular pressure (dP/dt) (0.0001<P< .001 versus control, calcium 1.5 mmol/L). After 30 minutes, tracer retention was 51.6%+/-6.1% injected dose (ID)/g and 54.2%+/-10.2% ID/g for control hearts perfused with 1.5 mmol/L and 0.75 mmol/L calcium, respectively (P = not significant). Myocardial activity of Tc-99m N-NOET was not modified in hearts perfused with verapamil (50.0%+/-4.1% ID/g), diltiazem (47.2%+/-8.7% ID/g), or nifedipine (51.7%+/-3.4% ID/g; P = not significant versus control hearts perfused with 1.5 mmol/L or 0.75 mmol/L calcium). CONCLUSIONS: Verapamil, diltiazem, and nifedipine were not responsible for any variations in Tc-99m N-NOET uptake and retention in the isolated rat-heart model. This might be explained by the binding of the tracer to endothelial cells, which do not present voltage-dependent calcium channels.

Animals↗
PubMed1990

Influence of pulsatile perfusion upon renin release from the isolated perfused rat kidney.

It is well established that renin release from the juxtaglomerular epithelioid cells in the media of the afferent arteriole strongly depends on the mean renal perfusion pressure, whereas a possible influence of the pulsation of blood pressure on renin release has only occasionally been investigated, and the results are contradictory. Such an influence on renin release cannot be excluded because pulsation is known to modulate arterial baroreceptors and vascular tone in some resistance vessels. In the isolated perfused rat kidney, we found a pulsation amplitude-dependent inhibition of renin release that could be blocked either by vasodilatation or by calcium channel blockade. The inhibition occurred at perfusion pressures between 85 and 125 mm Hg. The underlying pulsation pressure-sensitive mechanism has to be ascribed integrating properties, because a constant-flow pressure rise to the "systolic" value of pulsatile perfusion resulted in virtually the same inhibition of renin release. Moreover, a reduced urine flow during pulsatile perfusion provides evidence for preglomerular constriction under these conditions. It is concluded that, besides pathological changes of renal perfusion pressure, variations of the pulse amplitudes, e.g. resulting from renal artery stenosis or atherosclerosis, may also influence renin release and contribute to renovascular hypertension.

Animals↗
PubMed1988

Regulation of pancreatic polypeptide secretion in the isolated perfused human pancreas.

The isolated perfused human pancreas was used as a model to assess factors mediating the pancreatic polypeptide cell response to glucose, insulin, gastric inhibitory polypeptide, and splanchnic nerve stimulation. Pancreases obtained from 18 cadaveric organ donors were isolated and perfused by way of the splenic artery utilizing a Krebs bicarbonate buffer in a single-pass perfusion system. Hormonal stimulation and inhibition of pancreatic polypeptide secretion were assessed, as was the influence of direct electrical stimulation of celiac neural fibers innervating the pancreas. In this in vitro human model, pancreatic polypeptide cell secretion was inhibited by hyperglycemia, although the presence of gastric inhibitory polypeptide augmented the pancreatic polypeptide cell response. Perfusion with low levels of insulin and splanchnic nerve stimulation augmented the response of the pancreatic polypeptide cell to hyperglycemia and gastric inhibitory polypeptide. Since the immunoreactive pancreatic polypeptide response was augmented when insulin and somatostatin release was inhibited by perfusion insulin or nerve stimulation, we conclude that the pancreatic polypeptide cell is regulated by the ambient degree of somatostatin release, insulin release, or both. These findings support a centrifugal pattern of intraislet blood flow.

Adolescent↗
PubMed1999

Study of the biotransformation of benfluron using the isolated perfused rat liver.

The isolated perfused rat liver method (IPRL) was used to find, isolate and identify further metabolites of Phase I and Phase II biotransformation of the potential cytostatic agent benfluron with special regard to the conjugation processes. Its pharmacokinetic profile during the perfusion was also estimated. The rat liver was isolated from the body and perfused in vitro using a recirculating perfusion system. Benfluron was added to the reservoir as a bolus in doses of 200, 100, 30 mg/kg of body weigh and 1 mg/perfusate volume and also as a continual infusion in a dose of 0.1 mg/min in separate series of experiments. The following metabolites formed during Phase I biotransformation were found in the perfusion liquid as well as in the bile: benfluron N-oxide, 9-hydroxy benfluron, demethylated 9-hydroxy benfluron, demethylated benfluron, and reduced benfluron. The major Phase II metabolite found in the bile samples was the glucuronide of 9-hydroxy benfluron. The pharmacokinetic profile of benfluron in IPRL indicated its main disposition and metabolic pathway, i.e. its rapid extraction from perfusate by the liver (t1/2 alpha = 3.76 min), 9-hydroxylation followed up O-glucuronidation and excretion to the bile. It was revealed that 12% of the total dose of the parent compound was excreted to the bile in the form of conjugates during the first hour of perfusion, 32% during 1.5 hour, and 70% during 2 hours after the administration of benfluron. The conjugates with glucuronic acid represented 96-98% of all metabolites found in the bile.

Animals↗
PubMed1967

Electron microscopic and biochemical study of lipoprotein synthesis in the isolated perfused rat liver.

The isolated perfused rat liver was used to study the 300-800 A electron-opaque bodies which had previously been described in the liver cell Golgi apparatus, smooth endoplasmic reticulum, and space of Disse. When the perfusion medium was enriched with linoleate, the number and electron opacity of these particles increased markedly. Sequential biopsies showed that they appeared first in the smooth surfaced terminal ends of the rough reticulum, the smooth endoplasmic reticulum proper, and the Golgi apparatus and later in the space of Disse. After 60 min of perfusion, particles of the same size and shape as those in the liver cells could be isolated in large numbers from the d < 1.006 fraction of the perfusate. Control livers perfused with an identical medium but without linoleate did not show these changes. Puromycin markedly depressed the production of 300-800 A particles by livers perfused with an oleate-rich medium; however, it did not interfere with the formation of large cytoplasmic droplets of neutral fat. In keeping with these findings, puromycin blocked the incorporation of oleate-(14)C into lipoprotein triglyceride isolated from the perfusate, but did not interfere with the appearance of the labeled fatty acid in tissue triglyceride. Puromycin also blocked the incorporation of leucine-(3)H into both tissue protein and perfusate lipoprotein. We concluded that the 300-800 A particles observed are, in all likelihood, very low density lipoproteins and that their formation is blocked by puromycin, presumably through interference with the synthesis of their apoprotein.

Animals↗
PubMed1984

Dopamine production by the isolated perfused rat kidney.

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 +/- 0.1 ng DA X min-1 X g wet weight-1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 +/- 0.06 ng DA X min-1 X g-1 and denervated kidneys excreted 1.0 +/- 0.07 DA X min-1 X g-1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 +/- 0.1 ng DA X min-1 X g-1 (p less than 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng X min-1 X g-1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 +/- 0.13 ng DA X min-1 X g-1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗