Influence of an Uremia-Associated Serum Factor on CNS α2-Adrenoceptors

The action of blood serum from uremic rats and chronically hemodialyzed patients was investigated for effects on α₂-adrenoceptors labeled with ³H-clonidine. Compared to blood sera of rats and patients with normal kidney function, uremic serum significantly inhibited specific ³H-clonidine binding. In saturation experiments the density and affinity of α₂-adrenoceptors for ³H-clonidine was lowered by uremic serum. Heating, or trypsin or lipase treatment of the serum did not affect this phenomenon. The effect of the patient's serum could likewise be demonstrated after hemodialysis treatment. The presence of an allosteric regulating substance for clonidine binding to adrenoceptors could at least partially explain the altered and attenuated action of this drug in renal insufficiency.     

Peripheral adrenoceptors in hypotension of hemodialyzed uremic patients.

Hypotension is a common problem in patients on hemodialysis. To further investigate this problem, the number of platelet alpha 2-adrenoceptors and the activity of lymphomonocyte beta 2-adrenoceptors were measured in 10 hemodialyzed patients with normal blood pressure and in 10 sex- and age-matched persistently hypotensive hemodialyzed patients. Density of alpha 2-adrenoceptors was assessed by the specific binding of 3H-yohimbine to intact platelets, while the function of beta 2-adrenoceptors was estimated by the production of cAMP after the exposure of lymphomonocytes to isoprenaline. The maximal number of alpha 2-adrenoceptors was increased in the hypotensive compared to the normotensive group (262.13 vs. 77.21 fmol/mg protein; p < 0.01). Plasma norepinephrine was higher in the hypotensive than in the normotensive uremic patients (640 +/- 195 vs. 344 +/- 156 pg/ml; p < 0.01). Plasma epinephrine did not differ in the two groups (90 +/- 30 vs. 94 +/- 24 pg/ml). The amount of cAMP, produced by stimulation of lymphomonocytes, was lower in the hypotensive than that in the normotensive uremic patients (7.7 +/- 2.4 vs. 15.6 +/- 5.4 pmol/10(6) cells; p < 0.002). The increased number of alpha 2-adrenoceptors together with a high level of norepinephrine and reduced activity of adenylate cyclase (coupled with beta 2-adrenoceptors) support the hypothesis that hypotension in the hemodialyzed uremic patients may be related to a defect in adrenoceptor coupling mechanisms.     

Plasma catecholamines and alpha- and beta-adrenoceptors in circulating blood cells in patients on continuous ambulatory peritoneal dialysis

Autonomic system dysfunction could be the cause of postural hypotension seen in patients on continuous ambulatory peritoneal dialysis (CAPD). To verify this hypothesis, we examined the alpha 2- and beta 2-adrenoceptors on blood cells after 1/2 h in the resting supine position with the peritoneal cavity filled for 2-3 h, as well as the response of plasma norepinephrine (NE), heart rate (HR) and mean arterial blood pressure (MAP) to 10 min of standing. Supine free and particularly conjugated NE levels were significantly higher in all uremic patients compared with controls. The postural test induced similar increases of MAP and HR in 8 diabetic, 11 nondiabetic patients and 23 controls, whereas 4 diabetic patients became hypotensive. Orthostasis caused a mean free NE increment of only 0.5 nmol/l in the latter patient group with mean NE responses of 1.45-1.65 nmol/l in the former 3 groups. The densities of platelet alpha 2-adrenoceptors (assessed by [3H] yohimbine binding) and of mononuclear leucocyte (MNL) beta 2-adrenoceptors determined by (-) (125I) iodocyanopindolol binding amounted to 160 +/- 50 and 1600 +/- 520 binding sites/cell, respectively, in controls and were unchanged in patients without postural hypotension. The 4 diabetic patients suffering from postural hypotension showed numerically higher beta 2-receptor numbers (2080 binding sites/cell), significantly increased alpha 2-receptor densities (280 binding sites/cell, p less than 0.05) and significantly increased MNL isoproterenol-stimulated adenylate cyclase activities (38 vs 24 pmol cAMP/10(6) MNL/10 min in controls, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

血液灌流对尿毒症患者血清IL-1β、CRP和TNF-α水平的影响

目的观察血液灌流对维持性血液透析尿毒症患者血清中IL-1β、CRP和TNF-α的影响,以期为临床工作提供理论支持。方法收集93例尿毒症患者,随机分为观察组（51例）与对照组（42例）,对照组应用常规治疗和血液透析,观察组在常规治疗基础上加用血液灌流治疗,观察二组治疗前、治疗后血清中IL-1β、CRP和TNF-α的改变。结果尿毒症患者血清中IL-1β、CRP和TNF-α的表达增高,观察组与对照组治疗后血清中IL-1β、CRP和TNF-α的表达均下降,但是观察组下降值明显高于对照组。结论尿毒症患者应用血液透析和血液灌流进行治疗,能明显降低血清中IL-1β、CRP和TNF-α的表达,改善炎性微循环,临床中可以积极应用。     

Antinociception by epidural and systemic alpha(2)-adrenoceptor agonists and their binding affinity in rat spinal cord and brain

This study was designed primarily to relate the antinociceptive and hemodynamic effects of clinically available alpha(2)-adrenoceptor agonists to their binding affinity for alpha(2)-adrenoceptors in the spinal cord and brain. In rats with chronic indwelling epidural catheters, the percentage maximal possible effect on tail-flick latency was measured after epidural or IM dexmedetomidine (DXM), clonidine (CL), or tizanidine (TZ) administration. To examine their binding affinities, isolated spinal cord and brain membranes with an alpha(2) agonist were incubated with (3)H-UK14304, a selective alpha(2) agonist, and the radioactivity in the reaction mixtures was measured by liquid scintillation spectrometry. Epidural DXM (0.5-10 microg), CL (10-500 microg), and TZ (5-500 microg) all produced dose-dependent antinociceptive effects; the rank order of potencies was DXM > CL > TZ, the same as for their systemic administration. The antinociceptive effects were blocked by epidural yohimbine. The receptor binding affinities expressed as the concentration that inhibits 50% for spinal cord and brain, respectively, were 0.25 and 1.3 nM (DXM), 10.8 and 12.5 nM (CL), and 48.2 and 96.8 nM (TZ). The changes in arterial blood pressure and heart rate evoked by antinociceptive doses did not correlate with the rank order of antinociceptive potencies. The relative antinociceptive potencies of epidural alpha(2) agonists may depend on their binding affinities to alpha(2)-adrenoceptors in the spinal cord, but their cardiovascular effects may result from actions both inside and outside the central nervous system. IMPLICATIONS: Spinal antinociception caused by the epidural administration of alpha(2) agonists is well correlated with their binding affinity to spinal alpha(2)-adrenoceptors.     

In vitro alpha-adrenoceptor autoradiography of the urethra and urinary bladder of the female pig, cat, guinea-pig and rat

OBJECTIVE: The aim of this study was to investigate the distribution of alpha1- and alpha2-adrenoceptors in the urethra and urinary bladder of the female pig, cat, guinea-pig and rat. MATERIALS AND METHODS: The binding distributions of an alpha1-adrenoceptor ligand (3H-prazosin) and an alpha2-adrenoceptor ligand (3H-rauwolscine) were determined using in vitro autoradiography. Autoradiograms were analysed by combining computer-based image analysis and light microscopy. RESULTS: In the pig, guinea-pig and rat urethra 3H-prazosin binding was highest in the muscle layer. In the cat urethra 3H-prazosin binding could not be analysed due to a negative chemography artefact. In the pig, cat and guinea-pig urethra 3H-rauwolscine binding was highest in the urothelium, followed by the sub-mucosa, with low levels in muscle. Little 3H-rauwolscine binding was observed in the rat urethra. In the urinary bladder of all species 3H-prazosin binding was low. In the rat bladder, binding was higher in the trigone than in the dome. In the pig, cat and guinea-pig bladder 3H-rauwolscine binding was highest in the mucosa. with little binding in muscle or lamina propria. In the rat bladder, there was little binding and no regional differences. CONCLUSIONS: Alpha1-adrenoceptors were predominantly located in urethral smooth muscle, indicating their contractile importance in maintaining continence. Alpha2-Adrenoceptors were present in the urethral submucosa and bladder mucosa, but not in muscle, suggesting a role in regulation of blood flow, urethral lubrication and tumescence, but not in contraction.     

Pharmacokinetics of ropivacaine in uremic and nonuremic patients after axillary brachial plexus block

Reports on the efficacy and pharmacokinetics of local anesthetics in uremic patients have been controversial. Our study involved 29 uremic and 28 nonuremic patients. We performed axillary block with ropivacaine 300 mg (50 mL). Venous blood samples were drawn for 24 h for assay of total and unbound plasma ropivacaine, 3-hydroxyropivacaine, pipecoloxylidide (PPX), and serum alpha(1)-acid glycoprotein (AAG). Block quality was similar in both groups. No toxicity occurred. Plasma clearance of ropivacaine was smaller and the area under the concentration-time curve of ropivacaine, 3-hydroxyropivacaine, and PPX larger in the uremic patients. The plasma concentration of PPX increased until 24 h in uremic patients whose AAG concentrations were also larger throughout the study. The free fraction of ropivacaine in plasma was smaller in the uremic group when measured 60 min and 12 h after the block, but the unbound concentration of ropivacaine was larger in the uremic group at 12 h. Enhanced absorption of ropivacaine into circulation, increased binding to AAG, and probably reduced urinary excretion of the metabolites lead to larger total plasma concentrations of ropivacaine and its main metabolites in uremic patients.     

Artery calcification in uremic rats is increased by a low protein diet and prevented by treatment with ibandronate

The present experiments investigate medial artery calcification in adult rats made uremic by feeding a synthetic diet containing 0.75% adenine for 4 weeks. Calcification was assessed by Alizarin red staining of intact aortas, by von Kossa staining of carotid artery sections, and by calcium and phosphate incorporated into the thoracic aorta. The major conclusions are as follows: Lowering the protein content of the diet from 25 to 2.5% dramatically increases the frequency and extent of medial artery calcification in uremic rats without significantly affecting the elevation in serum creatinine, phosphate, or parathyroid hormone. This observation suggests that low dietary protein intake could be a risk factor for medial artery calcification in uremic patients. Medial artery calcification in uremic rats is prevented by a dose of ibandronate that inhibits bone resorption. The observation suggests that bone resorption inhibitors could prevent artery calcification in uremic patients. Medial artery calcification in uremic rats correlates with increased serum bone Gla protein (BGP; osteocalcin), but not with serum matrix Gla protein or fetuin. This finding indicates that it could be of interest to examine the relation between serum BGP and artery calcification in uremic patients. Each of these conclusions lends support for our hypothesis that medial artery calcification is linked to bone resorption. Future investigations of the as yet unknown biochemical basis for this link will be facilitated by the present discovery that a synthetic, 2.5% protein diet containing 0.75% adenine produces consistent and dramatic medial calcification in adult rats within just 4 weeks.     

The effects of nitric oxide synthase inhibitors on the sedative effect of clonidine.

The mechanism underlying the Niteroi, Rio de Janeiro sedative effect of clonidine, an alpha2-adrenoceptor agonist, remains uncertain. Because activation of alpha2-adrenoceptors induces release of nitric oxide (NO), we tested the hypothesis that the sedative effect of clonidine depends on NO-related mechanisms. The effect of 7-nitro indazole on the sleeping time induced by clonidine was studied in Wistar rats. In addition, we examined the effect of clonidine, alpha-methyldopa, and midazolam on the thiopental-induced sleeping time in rats pretreated with N(G)-nitro-L-arginine-methyl-ester (L-NAME). The sleeping time induced by clonidine was significantly decreased by 7-nitro indazole. Thiopental sleeping time was increased by clonidine, alpha-methyldopa, and midazolam. L-NAME reduced the prolongation effect of clonidine and alpha-methyldopa, but did not alter the effect of midazolam on the thiopental-induced sleeping time. The inhibitory effect of L-NAME on clonidine-dependent prolongation of thiopental-induced sleeping time was reversed by L-arginine. These results suggest that NO-dependent mechanisms are involved in the sedative effect of clonidine. In addition, this effect seems to be specific for the sedative action of alpha2-adrenoceptors agonists. IMPLICATIONS: Clonidine, an antihypertensive drug, is also a sedative. This sedative effect, although an adverse event in the treatment of hypertensive patients, can be helpful for sedation of surgical patients. The mechanism of this effect, however, is unknown. In this study, we show that the sedative effect of clonidine is mediated by nitric oxide, because it could be prevented by pretreatment with nitric oxide synthase inhibitors.     

Chronic triiodothyronine supplementation does not improve the lipoprotein disorders of mildly uremic rats

The present study was performed to appreciate the potential role that thyroid deficiency could play in the energy homeostasis and lipid metabolism of experimental chronic renal failure. For this purpose, 12 uremic rats that were supplemented with T3 (0.4 microgram/100 g body weight/day) during 5 weeks by means of osmotically driven minipumps were compared to 12 unsupplemented uremic rats and 12 control rats. The chronic supplementation of uremic rats with T3 induced no significant change in body weight gain or in the serum concentration of insulin, glucose, glycerol, nonesterified fatty acids, total triglycerides (TG), total cholesterol, and total choline phospholipids. Similarly, the metabolism of TG-rich lipoproteins was not affected by the supplementation with T3 in these uremic rats as appreciated by TG production or TG degradation (adipose tissue lipoprotein lipase activity). T3 administration induced a significant decrease in serum beta-hydroxybutyrate concentration and an increase in serum lactate concentration. Furthermore, heparin-releasable hepatic TG lipase activity as expressed per total liver mass was decreased in uremic rats treated with T3. The latter changes were observed in the absence of modifications of serum glucose or TG concentration. We conclude from these observations that rats with a moderate degree of chronic uremia do not seem to have a cellular thyroid deficiency sufficient to disturb their energy or lipid metabolism.     

Dialyzable factors from uremic serum increase 125I-fibrinogen binding by normal blood platelets

The influence of uremic serum on 125I-fibrinogen binding by normal blood platelets after induction with adenosine diphosphate was evaluated. The study was performed on 12 hemodialyzed uremic patients. The control group included 12 healthy subjects. It has been demonstrated that the uremic serum from the patients before hemodialysis significantly augmented fibrinogen binding by normal blood platelets (33.8 +/- 11.8%) in comparison with control subjects (14.4 +/- 8.9%). After hemodialysis, fibrinogen binding was comparable with the control group (14.9 +/- 10.1%). Uremic toxins removable during hemodialysis are probably responsible for the potentiation of 125I-fibrinogen binding by platelets.     

The alpha 1- and alpha 2-adrenoceptor selectivity of drugs with potential effects on blood pressure--a radioligand-binding study

In screening compounds with potential antihypertensive properties, the determination of their relative selectivities for alpha 1- and alpha 2-adrenoceptors is important not only for the elucidation of their mechanisms of action but also, possibly, for the assessment of their potential side-effects. The relative selectivity of a number of drugs for alpha 1- and alpha 2-adrenoceptors was determined by means of radioligand-binding studies. The alpha-adrenoceptor antagonists prazosin and indoramin display selectivities for alpha1-adrenoceptors of about factors 1 000 and 4 000 respectively. The alpha-adrenoceptor agonists clonidine and 2-(3,4-dihydroxyphenylimino)-imidazoline (DPI) display selectivities for alpha 2-adrenoceptors of about factors 200 and 300 respectively. The alpha-adrenoceptor antagonist mianserin displays approximately equal, albeit relatively low, affinities for alpha 1- and alpha 2-adrenoceptors. In view of the distribution of alpha 1- and alpha 2-adrenoceptors in vascular smooth muscle and in the reflex arcs controlling blood pressure, the low incidence of reflex tachycardia associated with the use of prazosin and indoramin can be explained on the basis of their alpha 1-adrenoceptor selectivity. Similarly, the hypertensive crisis which may follow the withdrawal of clonidine can be explained on the basis of a selective alpha 2-adrenoceptor agonistic action. The finding that mianserin has such low affinities for both alpha 1- and alpha 2-adrenoceptors may explain why, at therapeutically effective antidepressant dosages, it is usually devoid of adverse haemodynamic effects.     

Role of parathyroid hormone in the downregulation of liver cytochrome P450 in chronic renal failure

Chronic renal failure (CRF) is associated with a decrease in drug metabolism secondary to a decrease in liver cytochrome P450 (P450). The predominant theory to explain this decrease is the presence of factors in the blood of uremic patients. This study tested the hypothesis that parathyroid hormone (PTH) could be this factor. The objectives of this study were to determine (1) the role of PTH in the downregulation of hepatocyte P450 induced by rat uremic serum, (2) the role of PTH in the downregulation of liver P450 in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes. For this purpose, (1) hepatocytes were incubated with serum from rat with CRF that was depleted with anti-PTH antibodies or with serum from parathyroidectomized (CRF-PTX) rat with CRF, (2) the effect of PTX on liver P450 was evaluated in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes were determined. The depletion of PTH from CRF serum completely reversed the downregulating effect of CRF serum on P450 in hepatocytes. Addition of PTH (10(-9) M) to depleted CRF serum induced a decrease in P450 similar to nondepleted CRF serum. The serum of CRF-PTX rats had no effect on P450 in hepatocytes compared with CRF serum. Adding PTH to CRF-PTX serum induced a similar decrease in P450 as obtained with CRF serum. Finally, PTX prevented the decrease of liver P450 in rats with CRF. In summary, PTH is the major mediator implicated in the downregulation of liver P450 in rats with CRF.     

Inhibitory effect of oral sorbent on accumulation of albumin-bound indoxyl sulfate in serum of experimental uremic rats

Serum indoxyl sulfate, which is markedly accumulated in uremic patients, cannot be removed efficiently by hemodialysis due to its albumin binding. To determine if oral adsorbent (AST-120) can decrease its serum concentration in uremic state, oral adsorbent was administered to experimental nephrectomized uremic rats. Uremic rats fed with oral adsorbent showed a significantly lower serum concentration of indoxyl sulfate compared to control uremic rats, even when serum concentrations of urea nitrogen and creatinine were not significantly decreased in the uremic rats fed with oral adsorbent. Indoxyl sulfate was detected only at a lower concentration in bile as compared with the serum of uremic rats. These results suggest that oral adsorbent adsorbs indole, a precursor of indoxyl sulfate, in the intestine and prevents the accumulation of indoxyl sulfate in uremic rats.     

Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects of etomidate

BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific alpha2-adrenoceptor agonists of the type such as dexmedetomidine. The current study was performed to elucidate the possible interaction of etomidate with alpha2-adrenoceptors in mice lacking individual alpha2-adrenoceptor subtypes (alpha2-KO). METHODS: Sedative and cardiovascular responses to etomidate and the alpha2-agonist, dexmedetomidine, were determined in mice deficient in alpha2-receptor subtypes. Inhibition of binding of the alpha2-receptor antagonist [3H]RX821002 to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro. RESULTS: In vivo, loss and recovery of the righting reflex required similar times after intraperitoneal injection of etomidate in wild-type and in alpha2A-receptor-deficient mice, indicating that the hypnotic effect of etomidate in mice does not require the alpha2A-receptor subtype. Intravenous injection of etomidate resulted in a transient increase (duration 2.4 +/- 0.2 min) in arterial blood pressure in wild-type mice (17 +/- 3 mmHg). Etomidate did not affect blood pressure in alpha2B-KO or alpha2AB-KO mice. In membranes from HEK293 cells transfected with alpha2-receptors, etomidate inhibited binding of the alpha2-antagonist, [3H]RX821002, with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm). In alpha2B-receptor-expressing HEK293 cells, etomidate rapidly increased phosphorylation of the extracellular signal-related kinases ERK1/2. CONCLUSIONS: These results indicate that etomidate acts as an agonist at alpha2-adrenoceptors, which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure. This effect of etomidate may contribute to the cardiovascular stability of patients after induction of anesthesia with etomidate.     

Uremic serum effects on peripheral blood mononuclear cell and purified T lymphocyte responses.

We have studied the effects of uremic serum on the activation state and function of normal lymphocytes in vitro, by examining both accessory cell-dependent and accessory cell-independent responses. Uremic serum was obtained from patients on conservative treatment and from the same patients after they have undergone six months of maintenance hemodialysis. Uremic serum inhibited the proliferative responses to mitogens and to recombinant IL-2 (rIL-2) of both peripheral blood mononuclear cells (PBMC) and purified T cell populations. However, the responsiveness to IL-2 of pre-formed lymphoblasts, obtained from both PBMC and purified T cells, in the presence of uremic serum was similar to that obtained in the presence of normal serum, or was even enhanced. Uremic serum did not affect the cellular IL-2 receptor alpha (IL-2R) generation though it inhibited significantly the release of soluble IL-2 receptor (sIL-2R) and the production of IL-2 after mitogenic stimulation. Uremic serum from patients after six months of hemodialysis enhanced, but did not completely restore, proliferative responses and IL-2 production by control PBMC. Neither IL-1 nor IL-2R, which are present at elevated concentrations in uremic serum, appeared to be responsible for serum effects on in vitro responses of control lymphocytes. In conclusion, our results indicate that uremic serum affects both accessory cell-mediated and accessory cell-independent normal T cell responses. Uremic serum inhibition of T cell proliferation is associated with down-regulation of IL-2 synthesis by lymphocytes and the induction of an abnormal state of activation of lymphoblasts which is further enhanced following chronic hemodialysis.     

Effects of 1 alpha,25- and 24R,25-dihydroxyvitamin D3 on aluminum-induced rickets in growing uremic rats

Rats were subjected to a two-stage subtotal nephrectomy or sham operation, and treated with aluminum (Al) or both aluminum and vitamin D3 metabolites for 5 weeks with a cumulative dose of 13.6 mg aluminum. Animals were injected with 3H-thymidine and 3H-proline. The following analyses were performed: quantitative histology of tibial metaphyses and cytomorphometric electron microscopy of osteoclasts, quantitative (ICP-spectroscopy) and qualitative determination (histochemical staining) of aluminum within organs, and serum biochemistry (Ca, P, Mg, vitamin D3 metabolites, alkaline phosphatase, urea). The following new facts of the aluminum-related bone disease became evident: (a) Application of aluminum to growing uremic rats induced rickets, whose major epiphyseal growth plate changes were 1 alpha,25(OH)2D3-dependent. Addition of 1 alpha,25(OH)2D3 prevented the formation of rachitic metaphysis, but failed to prevent osteoid accumulation on epiphyseal and metaphyseal trabecular surfaces. Moreover, calcitriol produced hyperosteoidosis and osteosclerosis in the same rats. Aluminum did not alter the function of osteoblasts, while osteoclasts seemed inactivated. (b) The development of rickets was associated with suppressed serum levels of 1,25(OH)2D3, reduced phosphorus level and the high content of aluminum in the bone, kidney, and liver. The addition of 24R,25(OH)2D3 markedly exaggerated the reduction of serum levels of calcitriol. We suggested that aluminum induces rickets in growing uremic rats, which consists of two components: vitamin D refractory osteomalacia and 1 alpha,25(OH)2D3-dependent epiphyseal growth plate changes.     

Effect of oral carnitine supplementation on disturbances of lipid metabolism in the uremic rat

Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid metabolism observed in hemodialysis patients. The present study was performed to investigate the effects of L-carnitine administration on the lipid metabolism of rats with experimental chronic renal failure as compared to normal rats. Three groups of rats were studied: the first had induced chronic uremia, the second was sham-operated and pair-fed with the first, and the third was sham-operated and fed ad libitum. Serum triglycerides were significantly higher in uremic rats than in control animals of both groups. In addition to triglycerides, serum total cholesterol and phospholipids were also increased in uremic rats. The fractional clearance rate of Intralipid [K2(%)] was decreased in uremic as compared to control animals. The in vivo oxidation of radiolabeled palmitate was lower in uremic than in ad libitum-fed control animals but not lower than in pair-fed control rats. The daily oral administration of L-carnitine to uremic rats was associated with stable serum triglycerides. On the contrary, serum triglycerides increased significantly in the untreated uremic rats over the same period of time. Serum total cholesterol and phospholipids remained similar in the presence and the absence of L-carnitine treatment. The intravenous fat tolerance test of carnitine-supplemented uremic rats improved slightly, although not significantly, when compared to that of untreated uremic rats. In conclusion, oral L-carnitine supplementation in chronically uremic rats had only modest or no effects on several plasma lipid parameters.(ABSTRACT TRUNCATED AT 250 WORDS)