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PubMed1986

Net absorption of glucose, L-lactate, volatile fatty acids, and nitrogenous compounds by bovine given abomasal infusions of starch or glucose.

Three experiments were conducted to evaluate effects of abomasal infusion of glucose or starch on absorption of metabolites (glucose, L-lactate, volatile fatty acids, and nitrogenous compounds) from portal-drained viscera of a nonlactating Holstein cow and two Hereford X Angus heifers. Portal blood and plasma flow were determined by dilution of para-aminohippuric acid. Net absorption was portal-arterial concentration difference times portal plasma flow. Plasma concentration and portal-arterial difference of glucose increased rapidly and directly in response to increased rates of abomasal glucose infusion in the cow (Experiment 1). In the cow (Experiment 2), net absorption of L-lactate was greater with carbohydrate than with water infusion; net absorption of L-lactate was greater and of n-butyrate was less with starch than with glucose infusion. These responses were not evident in the heifers (Experiment 3). Net absorption of alpha-amino-N in the heifers was greater with starch than with glucose infusion. Increased concentrate intake by the heifers did not interact with responses to abomasal infusions. Recovery of infused glucose as absorbed glucose was similar for the cow and the heifers (65%). However, heifers absorbed (as glucose) 35% of infused starch and the cow only 8%.

Abomasum↗
PubMed1989

Nephrotoxicity of 5-(N-phenylcarboxamido)-2-thiobarbituric acid in the Fischer 344 rat.

In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease in p-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2 x MELD(10) (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i.e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity.

Alanine Transaminase↗
PubMed2004

Uric acid and the state of the intrarenal renin-angiotensin system in humans.

BACKGROUND: Experimental hyperuricemia is marked by an activated intrarenal renin-angiotensin system (RAS). The renal vascular response to exogenous angiotensin II (Ang II) provides an indirect measure of intrarenal RAS activity. We tested the hypothesis that the serum uric acid concentration predicts the renal vascular response to Ang II. METHODS: A total of 249 subjects in high sodium balance had the renal plasma flow (RPF) response to Ang II measured. Para-aminohippuric acid (PAH) clearance was used to estimate RPF. Multivariable regression analysis determined if the serum uric acid concentration independently predicts the RPF response to Ang II. Variables considered included age, gender, race, body mass index (BMI), hypertension status, blood pressure, basal RPF, creatinine clearance, serum insulin, serum glucose, serum high-density lipoprotein (HDL), serum triglycerides, and plasma renin activity (PRA). RESULTS: Uric acid concentration negatively correlated with the RPF response to Ang II (r=-0.37, P < 0.001). In univariate analysis, age, BMI, hypertension, triglycerides, and blood pressure were negatively associated, and basal RPF, HDL, and female gender were positively associated with the RPF response to Ang II. In multivariable analysis, serum uric acid concentration independently predicted the RPF response to Ang II (beta=-5.3, P < 0.001). CONCLUSION: Serum uric acid independently predicted blunted renal vascular responsiveness to Ang II, consistent with results from experimental hyperuricemia showing an activated intrarenal RAS. This could be due to a direct effect of uric acid or reflect a more fundamental renal process. These data may have relevance to the association of uric acid with risk for hypertension and nephropathy.

Adult↗
PubMed1997

Quantitative evaluation of brain distribution and blood-brain barrier efflux transport of probenecid in rats by microdialysis: possible involvement of the monocarboxylic acid transport system.

This study was performed to evaluate quantitatively the brain distribution and the efflux transport across the blood-brain barrier of probenecid, using in vivo microdialysis and in situ brain perfusion techniques. The brain interstitial fluid (ISF)-to-plasma cerebrospinal fluid (CSF)-to-plasma and brain tissue-to-plasma unbound concentration ratios of probenecid at steady state were less than unity, which suggests restricted distribution in the brain. An uphill concentration gradient from ISF to plasma and a downhill concentration gradient from CSF to ISF were observed. Kinetic analysis revealed that the efflux clearance from brain ISF to plasma (0.0373 ml/min/g brain) was significantly greater than the influx clearance from plasma to brain (0.00733 ml/min/g brain). The ratio of the ISF concentration (Cisf) to the plasma unbound concentration (Cp,f) of probenecid was increased 2- to 3-fold by salicylate (3.7 mM) and benzoate (3.6 mM), which are accepted as substrates of the monocarboxylic acid transport system, compared with the same ratio for the control. In addition, the ratio Cisf/Cp,f was increased by treatment with N-ethylmaleimide, a sulfhydryl-modifying agent, whereas p-aminohippuric acid and choline did not produce increasing effects on Cisf/Cp,f. These data suggest that the restricted distribution of probenecid in the brain may be ascribed to efficient efflux from the brain ISF, which may be regulated by the monocarboxylic acid transport system at a relatively high ISF concentration.

Animals↗
PubMed1993

Renal clearance of domoic acid in the rat.

The renal clearance (Clr) of the seafood toxin domoic acid (DA) was investigated in the rat. Following cannulation of the right femoral artery, the left femoral vein and the bladder of anaesthetized rats, a single bolus injection of either [3H]DA, [14C]p-aminohippuric acid (PAH) or [3H]inulin was administered through the venous cannula. Blood samples were taken from the arterial cannula at 1, 2, 10, 30, 50, 70, 90, 110 and 130 min following injection, and urine samples were collected at 20-min intervals starting from the time of bolus injection. Based on plasma concentration-time profiles, the total clearances (Clt) for DA, PAH and inulin were 9.12, 33.17 and 7.50 ml/min/kg body weight, respectively. The Clr calculated from urinary excretion rates were not significantly different from the Clt. Probenecid significantly reduced the Clr of PAH but did not affect that of DA. When DA was given at doses of 0.5 ng, 0.5 mg and 2.0 mg/kg body weight, the pharmacokinetic parameters Clt, Clr, elimination-rate constant and apparent volume of distribution at steady state were not statistically different between doses. The entire dose of 3H was recovered in the urine by 160 min after dosing, and analysis of urine samples by HPLC confirmed that the radiolabel (3H) was associated predominantly with the parent form of DA. The results of the present study demonstrate that DA is cleared from plasma primarily through the kidneys. DA clearance occurs primarily by renal glomerular filtration since its Clt is comparable with that of inulin, is less than that of PAH and is not affected by probenecid.

Animals↗
PubMed2001

Dopamine D2-like receptors and amino acid-induced glomerular hyperfiltration in humans.

AIMS: In rodents, blockade of dopamine D2-like receptors abolishes both the physiological increase in glomerular filtration rate (GFR) induced by amino acids and the pathological hyperfiltration in experimental diabetes mellitus. This study addressed the contribution of dopamine D2-like receptors to changes in renal haemodynamics after amino acid infusion in humans. METHODS: Twelve healthy volunteers participated in this double-blind, randomized, cross-over study. GFR and renal blood flow (RPF) were assessed by renal clearance of inulin and p-aminohippuric acid (PAH), respectively. Following infusion of 0.45% saline at baseline, an electrolyte-balanced solution of mixed amino acids (10%) was infused. Prior to the experiments, the subjects received orally either placebo, or sulpiride (10 mg kg-1), a centrally and peripherally acting D2-like receptor antagonist, or domperidone (1 mg kg-1) which affects only peripheral D2-like receptors. RESULTS: In the placebo series, amino acid infusion significantly increased GFR and RPF by up to 15.8 +/- 5.3% and 14.4 +/- 6.1%, respectively, while mean blood pressure and heart rate remained unchanged. Pretreatment with domperidone only marginally altered the renal response to amino acids (maximal increase by 13.2 +/- 5.6 and 11.9 +/- 4.0% in GFR and RPF, respectively), while sulpiride completely abolished the renal haemodynamic changes induced by amino acids. Total and fractional urinary sodium excretion as well as urinary osmolality were similar at baseline and increased in response to amino acids, to the same extent, in all series. No changes in renal dopamine excretion occurred. CONCLUSION: The results indicate that in man dopamine D2-like receptors are involved in the renal haemodynamic response to amino acid infusion. Whether dopamine D2-like receptor blockade diminishes glomerular hyperfiltration in pathological states requires clinical investigations.

Adult↗
PubMedDate not supplied

Binding of organic compounds to rat liver and lung.

The binding of various radioisotopically labeled organic compounds to rat liver and lung was investigated in vitro. Pieces of rat lung and slices of rat liver were incubated at 37 degrees C under a nitrogen atmosphere in a modified Krebs-Ringer phosphate solution (pH 7.4) CONTAININg the compound to be studied. Of the neutral compounds investigated, digitoxin, digoxin and dexamethasone were highly bound to both liver and lung tissue, whereas the degree of binding of amitrole, erythritol, and ouabain was 20% or less. The weak acids which were bound to the greatest extent in both liver and lung were phenobarbital, pentobarbital, and diphenylhydantoin. Barbital was poorly bound, and there was no evidence for the binding of 5,5-dimethyloxazolidine-2,4-dione or p-aminohippuric acid in either tissue. Binding of the cardiac glycosides and the barbiturates directly paralleled their lipid solubilities. The degree of binding of neutral compounds and weak acids to lung and liver tissue did not vary greatly with concentration, even though broad concentration ranges were studied. This was also true of the weak base morphine. On the other hand, the binding to liver and lung of the organic bases nicotine, pilocarpine, d-amphetamine, lidocaine, erythromycin, and chloroquine, did vary with concentration. The quaternary ammonium compound decamethonium was bound only to liver, and this binding also varied with concentration. Two additional quaternary ammonium compounds, tetraethylammonium and N1-methylnicotinamide, were not significantly bound to either tissue. Comparisons on the basis of equal content of solids revealed that the binding of diverse organic compounds in liver is greater than or equal to that in lung.

Amitrole↗
PubMed1988

Renal microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid.

Arachidonic acid is oxidized by the microsomal cytochrome P-450 monooxygenases of rabbit kidney cortex and medulla to products that include W and W-1 alcohols and several epoxyacids. In vivo administration of deoxycorticosterone acetate results in a time dependent and selective induction of the arachidonic acid W/W-1 oxygenase activity of cortex and medulla microsomal fractions (145% and 220% of controls, respectively). Initial segmental analysis shows the presence of an active epoxygenase activity in the isolated rabbit pars recta and its in vitro activation by p-aminohippuric acid.

Animals↗
PubMed1996

Precision-cut dog renal cortical slices in dynamic organ culture for the study of cisplatin nephrotoxicity.

The dog is the non-rodent species the most often used in preclinical drug safety evaluation. In this study, we established a new system of precision-cut dog renal cortical slices, evaluated their biochemical, functional, and morphological integrity, and determined the effects of cisplatin (cis-diamminedichloroplatinum (II), CDDP), a very potent nephrotoxic antineoplastic agent used to treat a variety of solid tumors, on the viability and histopathology of slices. Precision-cut renal cortical slices were made perpendicular to the cortical-papillary axis. Slices were incubated in DMEM/Ham's F12 culture medium containing 1 g/L glucose, 2 mmol/L glutamine, and 2 mmol/L heptanoic acid at 37 degrees C in an atmosphere of 5% CO2-70% O2-25% N2 in dynamic organ culture. Our results showed that slices maintained ATP and GSH content, protein synthesis, Na(+)-dependent uptake of glucose inhibited by phlorizin, PAH (p-aminohippuric acid) uptake inhibited by probenecid, and TEA (tetraethylammonium) uptake inhibited by mepiperphenidol for at least 6 h of culture, and morphological integrity up to 24 h. After 6 h of exposure, CDDP induced vacuolation and cell necrosis in the epithelial tubular cells of slices with a concentration-related increase in extension but not in severity. The development of the lesions started in the proximal tubules and extended to the distal tubules. The location and the extension of the lesions confirmed the observations in dog kidneys after in vivo treatment with CDDP by the intravenous route. The concentration-related decrease in slice viability after 6 h exposure to CDDP was in keeping with the extension of the histopathological lesions in the renal parenchyma. The slice viability was unaffected up to 0.63 mmol/L CDDP. At 1.25 and 2.5 mmol/L CDDP, slice viability fell by 35% and 75%, respectively. These results suggest that precision-cut dog renal cortical slices in culture may be suitable for addressing the specific nephrotoxicity issues encountered in this species.

Animals↗
PubMed2005

NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice.

Sepsis is a severe catabolic condition. The loss of skeletal muscle protein mass is characterized by enhanced release of the amino acids glutamine and arginine, which (in)directly affects interorgan arginine and the related nitric oxide (NO) synthesis. To establish whether changes in muscle amino acid and protein kinetics are regulated by NO synthesized by nitric oxide synthase-2 or -3 (NOS2 or NOS3), we studied C57BL6/J wild-type (WT), NOS2-deficient (NOS2-/-), and NOS3-deficient (NOS3-/-) mice under control (unstimulated) and lipopolysaccharide (LPS)-treated conditions. Muscle amino acid metabolism was studied across the hindquarter by infusing the stable isotopes L-[ring-2H5]phenylalanine, L-[ring-2H2]tyrosine, L-[guanidino-15N2]arginine, and L-[ureido-13C,2H2]citrulline. Muscle blood flow was measured using radioactive p-aminohippuric acid dilution. Under baseline conditions, muscle blood flow was halved in NOS2-/- mice (P < 0.1), with simultaneous reductions in muscle glutamine, glycine, alanine, arginine release and glutamic acid, citrulline, valine, and leucine uptake (P < 0.1). After LPS treatment, (net) muscle protein synthesis increased in WT and NOS2-/- mice [LPS vs. control: 13 +/- 3 vs. 8 +/- 1 (SE) nmol.10 g(-1).min(-1) (WT), 18 +/- 5 vs. 7 +/- 2 nmol.10 g(-1).min(-1) (NOS2-/-); P < 0.05 for LPS vs. control]. This response was absent in NOS3-/- mice (LPS vs. control: 11 +/- 4 vs. 10 +/- 2 nmol.10 g(-1).min(-1)). In agreement, the increase in muscle arginine turnover after LPS was also absent in NOS3-/- mice. In conclusion, disruption of the NOS2 gene compromises muscle glutamine release and muscle blood flow in control mice, but had only minor effects after LPS. NOS3 activity is crucial for the increase in muscle arginine and protein turnover during early endotoxemia.

Animals↗
PubMed1992

Protection from hypoxemia-induced renal dysfunction by the thiophosphate WR-2721.

The acute renal effects of hypoxemia-reoxygenation and the putative protective action of WR-2721 [S-, 2-(3-aminopropyl-amino)-, etylphosphosphorothioic acid], a drug with specific properties such as PTH-secretion inhibiting, calcium lowering and free radical scavenging activities, were investigated in anesthetized-ventilated rabbits. Glomerular filtration rate (GFR) and renal blood flow (RBF) were assessed by the clearance of inulin and para-aminohippuric acid, respectively. Each animal acted as its own control. Normoxemic control rabbits showed no changes in renal hemodynamics and function during 150 minutes. The administration of WR-2721 (75 mg/kg body wt i.v.) to normoxemic animals induced a significant decrease in MBP, RBF and diuresis, without affecting GFR. It significantly reduced plasma levels of PTH, decreased calcemia and increased urinary calcium excretion. In untreated hypoxemic-reoxygenated rabbits, 45 minutes of severe hypoxemia (PO2 around 35 mm Hg) induced a significant fall in MBP, GFR, RBF and diuresis, which persisted during the 60-minute reoxygenation period. The administration of WR-2721 before hypoxemia or reoxygenation prevented the hypoxemia-induced decrease in GFR and diuresis. Filtration fraction increased significantly. The renal functional improvement observed in hypoxemic rabbits administered WR-2721 could be mediated by its effect on calcium metabolism and/or its oxygen free radical scavenging properties.

Amifostine↗
PubMed1997

Hepatic amino acid and protein metabolism in non-anorectic, moderately cachectic tumor-bearing rats.

BACKGROUND/AIMS: Cancer cachexia is characterized by loss of lean body mass. Under this condition peripheral proteins are broken down and transferred to visceral organs and the tumor. The liver is the principal organ in the regulation of protein and amino acid metabolism, but liver amino acid kinetics in cancer are unclear. Therefore, we examined the effects of increasing tumor loads on hepatic protein turnover and amino acid handling. METHODS: A MCA-induced sarcoma was implanted subcutaneously in Lewis rats (200-225 g). Rats were studied when the tumor was 5-15% or 15-30% of body weight. Control rats were sham implanted. Under anesthesia, a primed constant infusion of para-aminohippuric acid and L-[3, 4-3H]-valine was given to calculate hepatic substrate fluxes and protein turnover. Serum alpha 2-macroglobulin concentration was measured to determine the acute phase response. RESULTS: Carcass weight decreased approximately 10% in large-tumor-bearing rats (p < 0.001). Liver wet weight increased from 5.5 +/- 0.1 (g) to 5.9 +/- 0.2 in the small-tumor-bearing group and 7.3 +/- 0.3 (p < 0.001) in the large-tumor-bearing group, with minimal changes in water content. Serum alpha 2-macroglobulin concentration, essential and gluconeogenic amino acid uptake by the liver increased in large-tumor-bearing animals. This contrasted with reduced liver ammonia uptake and unchanged urea production in tumor-bearing rats. In the small-tumor-bearing group liver protein synthesis increased, whereas protein breakdown remained unchanged. In the large-tumor-bearing group protein synthesis also increased, but protein breakdown decreased to zero. CONCLUSIONS: The study shows that in tumor-bearing rats, liver uptake of essential and gluconeogenic amino acids increases without significant increases in urea or glucose production. Synthesis of both structural and export proteins, e.g. acute phase proteins, increases suggesting that the liver becomes a more efficient nitrogen-sparing and active protein-synthesizing organ during the growth of a malignant tumor.

Amino Acids↗
PubMed2001

[Quantitative assay of metabolic rate of para-aminobenzoic acid combining glycine for the assessment of rabbit liver function].

OBJECTIVE: To evaluate liver function by the assessment of the capacity of glycine combining para-aminobenzoic acid (PABA) to form hippuric acid in rabbits with acute liver injury. METHODS: Thirty rabbits were randomly divided into two groups: experiment group (n=20) received D-galactosamine to be subject to acute liver necrosis, and control group (n=10) received saline as placebo. Serum concentrations of PABA, para-aminohippuric acid (PAHA), para-acetamidobenzoic acid (PAABA), and para-acetamidohippuric acid (PAAHA) were measured by high pressure liquid chromatography (HPLC). RESULTS: Compared with control group, the serum concentrations of PAHA and PAAHA were significantly reduced in experimental group, which were correlated with the degree of liver injury. CONCLUSIONS: The metabolic rate of glycine combining PABA is a sensitive index for quantitative test of liver function and assessment of acute liver necrosis.

4-Aminobenzoic Acid↗
PubMed1981

Structural specificity in the renal tubular transport of tyrosine.

The structural requirements for aromatic amino acid reabsorption and secretion in the dog were investigated using a series of tyrosine analogs. In clearance experiments, l-tyrosine and l-phenylalanine underwent net reabsorption at rates 5 to 6 times greater than those of the corresponding d-enantiomers and about 1.5 time those of o- and m-dl-tyrosine. 3-(p-hydroxyphenyl)Propionic acid underwent net secretion under conditions of polyuria and high urinary pH and net reabsorption under conditions of oliguria and low pH. In stop-flow experiments, (U/Pl-amino acid)/(U/Pln) ratios, where U/P = concentration in urine and plasma and In = inulin, of proximal tubular samples were 1.5 to 5-fold greater than the control (free-flow) values of 0.1 to 0.3, indicating tubular secretion. Secretion was inhibited, and net reabsorption enhanced, by probenecid, p-aminohippuric acid and 2,4-dinitrophenol. (U/Pd-amino acid)/(U/PIN) ratios of proximal tubular samples were below the control values of 0.6 to 0.8, indicating tubular reabsorption. Probenecid had no effect on the overall pattern but caused a slight decrease in the relative clearance values. The stop-flow pattern of 3-(p-hydroxyphenyl)propionic acid excretion was similar to that of the I-amino acids. It was concluded that the I-amino acids undergo bidirectional transport and that the I-configuration and amino group are required for optimal active reabsorption, whereas ring hydroxylation has little effect on reabsorption transport. No absolute structural requirements for active secretion were elucidated.

Absorption↗
PubMed1998

Efflux of taurocholic acid across the blood-brain barrier: interaction with cyclic peptides.

The mechanism for the efflux of taurocholic acid (TC) across the blood-brain barrier (BBB) was studied by examining the elimination of [3H]TC after microinjection into the cerebral cortex. The efflux of [3H]TC from the brain was saturable with a Vmax of 15.0 pmol/min/g brain and a Km value of 0.396 nmol/0.2 microl injectate. Efflux was inhibited by cholic acid (CA), a cationic cyclic octapeptide (octreotide; a somatostatin analogue) and an anionic cyclic pentapeptide (BQ-123; an endothelin receptor antagonist), with an IC50 value of 1.09 nmol/0.2 microl injectate, 1.12 nmol/0.2 microl injectate and 0.12 nmol/0.2 microl injectate, respectively. Probenecid (20 nmol/0.2 microl injectate), but not p-aminohippuric acid (10 nmol/0.2 microl injectate), inhibited the brain efflux of [3H]TC. In addition, elimination of [3H]BQ-123 after microinjection was saturable with a Vmax of 20.8 pmol/min/g brain and a Km of 2.92 nmol/0.2 microl injectate; it was also inhibited by TC with an IC50 value of 0.074 nmol/0.2 microl injectate. In contrast, no significant efflux of [14C]octreotide from the brain was observed until 60 min after microinjection. These results suggest that both TC and BQ-123 are transported from the brain to the circulating blood across the blood-brain barrier via specific mechanisms. Although mutual inhibition was observed between TC and BQ-123, kinetic analysis suggested that the two transport systems differ.

Animals↗
PubMed2005

The dietary polyphenol ellagic acid is a potent inhibitor of hOAT1.

Ellagic acid (EA), a polyphenol present in berries, has been demonstrated to be preventive of esophageal and colon cancer in animals. Here, we have studied the ability of organic anion transporters (OATs) and organic anion-transporting polypeptides (OATPs) to transport EA. The accumulation of radiolabeled (14)C]EA, [(3)H]p-aminohippuric acid (PAH), [(14)C]glutarate, [(3)H]estrone sulfate, [(3)H]ochratoxin A, and [(3)H]taurocholic acid +/- inhibitor(s) was tested in OAT- and OATP-expressing oocytes. Oocytes expressing human (h)OAT1, rat (r)Oat1, and hOAT4 accumulated 6.5-, 7.1-, and 8.9-fold more EA, respectively, than did water-injected oocytes. This accumulation was prevented by the prototype OAT inhibitors bromosulfophthalein and probenecid. rOatp1, mouse (m)Oat2, hOAT3, and mOat5 showed no EA transport. The uptake of the prototype OAT substrate PAH in hOAT1-expressing oocytes was dose dependently and potently inhibited by EA with an IC(50)of 207 nM. In conclusion, we have demonstrated that the OAT family members hOAT1, rOat1, and hOAT4 mediate transport of EA, with a very high affinity for hOAT1.

Animals↗
PubMed1982

Effect of L-dopa on renal handling of uric acid.

Several reports have indicated that L-dopa may cause hyperuricemia and gout. The reports of hyperuricemia have generally been explained on the basis that L-dopa is known to produce a false hyperuricemia by interfering in the colorimetric analysis of uric acid. Our studies of the interference of L-dopa in the analysis of uric acid revealed that the false elevation of uric acid produced by therapeutic plasma concentrations of L-dopa is minor. The present studies used the Sperber in vivo chicken technique to determine whether L-dopa interferes with the renal excretion of uric acid. We found that a 440 mg/kg dose of L-dopa given by stomach tube results in a 30% decrease in the renal tubular excretory transport of [14C]uric acid. L-Dopa infused along with [14C]uric acid into the renal portal circulation also decreases the excretory transport of [14C]uric acid. In addition, i.v. L-dopa at 8.5 or 11.6 mumol/min/leg causes an increase in plasma urate of 26 or 45%, respectively. During infusion of L-[14C]dopa into the peritubular circulation, the 14C-label was excreted into the urine at a rate equivalent to 35% that of simultaneously infused p-aminohippuric acid or [3H] tetraethylammonium. The excretory transport of 14C-label was inhibited by probenecid. Because the renal tubular excretory transport of uric acid in chickens has many similarities to that of man, the results suggest that inhibition of uric acid excretory transport may be one of the effects of L-dopa, or its metabolites, in man.

Animals↗
PubMed1993

Use of a single injection solute-clearance method for determination of glomerular filtration rate and effective renal plasma flow in chickens.

A single-injection clearance method for determining glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in chickens was compared with the continuous-infusion method. Male and female White Leghorn chickens were anesthetized, and catheters were placed in both brachial veins and over both ureteral openings. A single-bolus injection of 3H-inulin and 14C-para-aminohippuric acid was given at a dose of 1.0 microCi of each solute per kg of body weight and nine blood samples were obtained over 60 min. After the last sample was taken, the birds were given a bolus injection of 1 microCi of 3H-inulin/kg and 1 microCi of 14C-para-aminohippuric acid/kg, followed by a constant infusion of 0.1 microCi of each solute/min at a rate of 0.1 ml.kg-1 x h-1. Following a 45-min stabilization period, three continuous urine collections were performed. A blood sample was obtained at the midpoint of each urine collection. The GFR and ERPF determined by the single-injection method (3.12 +/- 0.43 and 22.81 +/- 3.48 ml.min-1 x kg-1, respectively) were comparable to values for the continuous-infusion method (2.81 +/- 0.35 and 22.88 +/- 4.03 ml.min-1 x kg-1, respectively). Both GFR and ERPF determined by the single-injection method correlated with GFR and ERPF determined by the continuous-infusion method. This single injection method provides a rapid, accurate method for determining GFR and ERPF in chickens and eliminates the need for collection of urine.

Animals↗