Blood Cells Of Rats Research Articles

The in-vitro uptake of zinc by blood cells in rats with long-term inflammatory stress

The aim of the present study was to investigate the in vitro uptake of zinc by blood cells, in an attempt to distinguish between those conditions in which low plasma zinc concentrations are due to inflammatory stress, and those which are due to true zinc deficiency. Inflammation induced by intramuscular injection of turpentine caused a significant reduction in plasma albumin concentrations, which persisted until the end of the study (2 weeks). It also caused a reduction in the plasma zinc concentration which was most marked during the first few days. A smaller difference persisted until the end of the study. When the serum zinc concentration was corrected for the hypoalbuminaemia, the changes in serum zinc concentration after the first 4 days of turpentine were small and mainly non-significant. The in vitro uptake of zinc by erythrocytes obtained from animals with inflammation did not increase, whereas the uptake was increased in cells obtained from animals with true zinc deficiency. Therefore this study suggests a method that can probably differentiate between an apparent zinc deficiency due to inflammatory stress and a real zinc deficiency, but additional experiments to validate this method should be performed.

Calcium permeability and ATPase activities of red blood cells of magnesium deficient rats

Decreased intracellular magnesium and potassium and increased sodium levels were shown in the erythrocytes of weanling rats fed a low magnesium diet for 8 days. Magnesium-dependent ATPase activity was significantly increased in membranes obtained from Mg-deficient cells and the (Ca 2+-and (Na + + K +)-stimulated activities were similar to control values. Calcium flux measurements clearly show that passive permeability was significantly increased in red blood cells from Mg-deficient rats. Moreover, initial rates of calcium influx and to a lesser degree calcium efflux were increased in ghosts prepared from Mg-deficient erythrocytes. In agreement with our previous findings on the physico-chemical parameters of these membranes, the present results strongly suggest that permeability properties rather than the pump activities are primarily affected by dietary magnesium deficiency.

Purification of endothelin-1 -inactivating peptidase from the rat kidney

To identify and purify endothelin-1-inactivating peptidase from rat tissues. Subcellular fractions of rat kidney, aorta, heart, lung, liver and blood cells were prepared by differential centrifugation. Kidney membrane-bound peptidase was solubilized with Triton X-100, chromatographed on the diethylaminoethyl-cellulose, ultrafiltered through a membrane of relative molecular mass 100,000 cutoff and subjected to electrophoresis on a non-denaturing polyacrylamide gel. The enzyme activity assay was performed at pH 5.5 using [125I]-endothelin-1 as the substrate. The trichloroacetic acid precipitation test, an endothelin-1 immunoreactivity assay, reverse-phase high-performance liquid chromatography and a receptor-binding assay were applied for the detection of degradation products. High-activity endothelin-1-degrading peptidase coincided with the fraction from the kidney membranes of both Wistar-Kyoto and spontaneously hypertensive rats, but not with any other of the tissues that were studied. The membrane (0.5 microgram protein/assay) degraded [125I]-endothelin-1 (5-100 pmol/l) within a half-time of about 10 min at 37 degrees C. The enzyme was purified to an apparent homogeneity with non-denaturing gel electrophoresis, by which it was identified as a low-mobility (Rf 0.07) protein fraction of high relative molecular mass (> 250,000). The optimum pH was 5.5, with a little activity found outside the range 5.0-7.0. The activity of the peptidase was inhibited by 0.5 mmol/l 1,10 phenanthroline (half-maximal inhibitory concentration 0.03 mmol/l), and by 1 mmol/l EDTA, implicating a metalloenzyme. Bestatin, puromycin, phenylmethylsulphonyl fluoride and thiorphan were without effect. Unlabelled endothelin-1 inhibited the degradation of [125I]-endothelin-1 (half-maximal inhibitory concentration 100 nmol/l), whereas 100 mumol/l methionine enkephalin or angiotensin I did not. High-performance liquid chromatography analyses of the [125I]-endothelin-1 incubated with purified peptidase revealed a time-dependent accumulation of one major radioactive fraction that was soluble in trichloroacetic acid. This product (or products) was not further hydrolysed. It did not react with the endothelin antibodies or with the specific, myocardial membrane receptors. Our data suggest that the rat kidney contains an acidic metalloproteinase of high relative molecular mass that is able to hydrolyse endothelin-1 rapidly and efficiently in vitro. The enzyme may participate in the inactivation of circulating or tissue endothelins, or both.

Effects of 2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) on Humoral Immunity and Lymphocyte Subpopulations: Differences Between Mice and Rats

While the effect that TCDD has on humoral immunity has been well documented for the mouse, it has not been for the rat. In this study, the effect that TCDD has on the antibody plaque-forming cell (PFC) response to sheep red blood cells (SRBC) in adult female B6C3F1 mice and F344 rats was compared. The effect that TCDD has on the PFC response of male F344 and female Long-Evans rats was also determined. Mice or rats were given a single intraperitoneal injection of TCDD at doses ranging from 0.1 to 30 μg/kg, 7 days prior to intravenous immunization with SRBC. Four days later the PFC response to SRBC was determined. Mice showed a dose-related suppression of the PFC response, with an ED50 of 0.7 μg/kg TCDD. In contrast, TCDD failed to suppress and in fact enhanced the PFC response to SRBC in rats at doses as high as 30 μg/kg. The inability of TCDD to suppress the PFC response in rats was unrelated to hepatic CYP1A1 and CYP1A2 induction which was detectable at doses of 1 and 0.3 μg/kg TCDD, respectively. There was no shift in the time to peak PFC response in rats dosed with TCDD, nor was the failure of TCDD to suppress the PFC response in rats related to gender or strain. Phenotypic analysis of thymocytes and splenic lymphocytes from TCDD-dosed (i.e., 3, 10, or 30 μg/kg) and SRBC-immunized mice and rats revealed that CD4 −CD8 + splenocytes were reduced in a dose-related manner in rats only and that this reduction in CD4 −CD8 + was accompanied by a dose-related increase in IgM + splenocytes. These results demonstrate species differences in the effect of TCDD on the PFC response to SRBC which were unrelated to hepatic CYP1A1 or CYP1A2 induction, time to peak response, gender, and strain. The failure of TCDD to suppress and in fact to enhance the PFC response to SRBC in rats appears to be related to alterations in splenic CD4 −CD8 + lymphocytes.

Pharmacokinetics of a New Benzimidazole Sulfoxide Derivative, E3810. (2): Absorption, Distribution, Metabolism and Excretion in Rats.

The absorption, distribution, metabolism and excretion of E3810 were studied in rats after administration of [benzimidazole-2-14C] E3810 (abbreviated as 14C-E3810) or [alpha methylene-14C] E3810. After a single intraduodenal dose of 14C-E3810 (20 mg/kg) to rats, the blood level of radioactivity reached maximum at 15 minutes (3.86μg eq./ml of blood) and then was eliminated extremely slowly. In rats, the radioactivities in blood cells and thyroid tissue remained for a long time following administration of 14C-E3810. On the other hand, radioactivities in these tissues after dosing of [alpha methylene-14C] E3810 were eliminated faster than after dosing of 14C-E3810. Therefore, the long half life time in blood cells and thyroid tissues after dosing of 14C-E3810 should be attributed to the moiety of benzimidazole ring labeled with 14C. After addition of 14C-E3810 to blood in vitro, the incorporation of 14C to blood cells in rats was higher than these in dogs and in humans. After intraduodenal administration of 14C-E3810, the radioactivity rapidly distributed to the tissues except for the thyroid and the distribution of radioactivity into the brain was very low. The radioactivity in the tissues were rapidly eliminated, except the blood cells and the thyroid. Distribution of radioactivity to gastric mucosa, the target tissue, after intravenous dose was shown clearly by the whole body autoradiography. The main metabolites in plasma were UM-1, and UM-2, with small amounts of unchanged compound, M-1, and M-2 at 15 minutes after dosing of 14C-E3810. In the hepatic portal vein, over 70% of the radioactivity was recovered as unchanged compound after intraduodenal dose in situ experiment, therefore it was suggested that E3810 is mainly metabolized in liver. The urinary and fecal excretions of radioactivity were 39.75% and 56.32% of dose, respectively for 8 days after intraduodenal administration of 14C-E3810 to rats. The biliary excretion of radioactivity was 60.86% of dose 24 hours after intraduodenal administration in bile duct-cannulated rats.

Accumulation of DNA adducts of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) in tissues and white blood cells of the Fischer-344 rat after multiple oral dosing.

The genotoxic effect of an environmental chemical may be estimated from the concentration of its DNA adducts in peripheral white blood cells (WBCs). The food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is carcinogenic in the Fischer-344 rat, affecting principally the liver, small intestine and large intestine. In the present study we have determined whether DNA adducts of IQ are present in circulating WBCs of rats after single or multiple oral doses of IQ and how these adducts are related to those in internal organs. Male Fischer-344 rats received IQ as an oral dose (5 or 50 mg/kg, starting on day 0) by daily gavage (1, 8 or 15 days of treatment). Using 32P-postlabeling assays, IQ-DNA adducts were isolated and quantitated in organs and WBCs on days 1, 8 and 15. Adduct patterns in WBCs were qualitatively similar to those in the organs and adduct formation was highest in the liver, followed by the lungs, kidneys, stomach, large intestine, WBC and small intestine. Accumulation of adducts occurred in all organs and in WBCs in a dose- and time-dependent manner. For all organs, IQ-DNA adduct formation was strongly correlated with those in WBCs. It is concluded that IQ-DNA adducts in WBCs are qualitatively and quantitatively directly related to those in internal organs, independent of the target organ specificity of the carcinogenic effect of IQ.

The effect of fenclofenac on the regeneration of lymphocytes in rats following total body irradiation

The effect of fenclofenac on the regeneration of white blood cells in Sprague-Dawley rats following total body irradiation was investigated. The lowest dose of total body irradiation that would suppress the peripheral blood lymphocyte count by at least 50% was found to be 1.0 Gray in a preliminary experiment. Fenclofenac in a dose of 150 mg/kg/day retarded the regeneration of lymphocytes following total body irradiation of 1 Gray: this effect was also seen in the CD4, CD8 and B-lymphocyte subsets. This suppressive effect in vivo may be due to interference with replicative growth of white blood cells since previous in vitro experiments have shown suppression of lymphocyte growth at a stage later than activation in the cell cycle. The suppression effects on leucocyte regeneration in vivo suggest that fenclofenac may have promise as an immunosuppressive drug with fewer serious side effects than the currently available immunosuppressive drugs.

Binding of Fluvastatin to Blood Cells and Plasma Proteins

The binding of fluvastatin, an inhibitor of hydroxymethylglutaryl coenzyme A reductase, to plasma proteins and red blood cells of rat, dog, and human in vitro was determined by ultrafiltration. Additionally, the stereospecificity of fluvastatin binding to proteins and the potential interaction between fluvastatin and the highly protein bound drugs warfarin, salicylic acid, and gfyburide were investigated. Only a small fraction of fluvastatin in blood was taken up by the blood cells, amounting to 19–33% in the rat and ≤ 15% in dog and humans. The plasma:blood fluvastatin ratio in these species at 37°C was ≥1.4. In human blood, this ratio was temperature independent, in the plasma concentration range 25–50 000 ng/mC fluvastatin was ≥98% bound to proteins. The binding was concentration dependent in the rat, but not In the dog and human. Both enantiomers of fluvastatin were >99% bound in normal human plasma, the binding of each being unaffected by the presence of the other. A major fluvastatin-binding protein in human plasma was albumin, whereas binding to α1-acid glycoprotein was relatively weak and concentration dependent. At therapeutic concentrations in normal human plasma, the protein binding of fluvastatin (0.1 μg/mL) was unaffected by warfarin (1–10 μg/mL), salicylic acid (50-150 μ/mL), and glyburide (0.1–1 μ/mL). Similarly, fluvastatin had no influence on the binding of these compounds. In diluted human albumin solution (29 μM), bound fluvastatin was displaced by all three co-solutes tested. The total binding constant of fluvastatin was reduced by ˜40%, 50%, and sevenfold in the presence of warfarin, glyburide, and salicylic add, respectively. Conversely, fluvastatin reduced the total binding constant of salicylic add by ˜34% but had little effect on the binding of warfarin and glyburide. The mutual inhibition between fluvastatin and salicylic add appears to be of the competitive type.

Cadmium-induced changes of antioxidant and metabolic status in red blood cells of rats: in vivo effects.

Chronic exposure of adult rats to dietary intake of cadmium (15 mg CdCl2/day/kg for 30 days) leads to development of anemia and thrombocytosis. Anemia is characterized by significant reticulocytosis (13.1 +/- 1.0%), anysocytosis, poikilocytosis, iron deficiency and marked alterations of antioxidant and metabolic status of red blood cells. Activities of SOD, catalase, GPx and GR were significantly increased in red blood cells of cadmium-treated rats. In treated animals cadmium induced an increase of red cell reduced and oxidized glutathione with no changes of GSSG/GSH ratio. However, significant reduction of lipid peroxidation was found. Plasma levels of tocopherol and ascorbate, as well as activity of glutathione-S-transferase, were all significantly increased in cadmium-treated rats. The energy metabolism of red blood cells was deeply altered in cadmium-treated rats. The levels of ATP, ADP, AMP and TAN were significantly increased while ATP/ADP ratio and adenylate energy charge (AEC) were significantly reduced. The level of 2,3-BPG was somewhat lower, but 2,3-BPG/Hb ratio was considerably higher, in red blood cells of cadmium-treated rats.

Tumour necrosis factor-α alters the blood compartmentation of amino acids in the rat

The work presented focuses on the importance of studying the distribution of blood amino acids in both the cellular and plasmatic fraction when performing studies concerning the effects of cytokines on amino acid metabolism. Tumour necrosis factor treatment resulted in important changes in blood amino acid compartmentation between plasma and red blood cells in rats. The animals showed a change in compartmentation with an increase in the concentration of most amino acids in the cellular fraction with the exception of phenylalanine, glutamate, aspartate and tyrosine.

Increased release of tumor necrosis factor-alpha into the cerebrospinal fluid and peripheral circulation of aged rats.

We earlier reported that risk factors for stroke prepare brain stem tissue for a modified Shwartzman reaction, including the development of ischemia and hemorrhage and the production of tumor necrosis factor-alpha, after a provocative dose of lipopolysaccharide. In the present study, we sought to determine whether blood and central nervous system cells of rats with the stroke risk factor of advanced age produce more proinflammatory and prothrombotic mediators than do those of young rats of the same strain. Levels of tumor necrosis factor-alpha and platelet activating factor in the cerebrospinal fluid and tumor necrosis factor-alpha in the serum of 2-year-old and 16-week-old Sprague-Dawley rats were monitored before and after challenge with lipopolysaccharide. No consistent tumor necrosis factor-alpha activity was found in the cerebrospinal fluid or blood of control animals. Intravenous administration of lipopolysaccharide (1.8 mg/kg) increased serum tumor necrosis factor-alpha levels but had no effect on tumor necrosis factor-alpha in the cerebrospinal fluid. Serum tumor necrosis factor-alpha increased much more in aged rats than in young rats. When lipopolysaccharide was injected intracerebroventricularly, tumor necrosis factor-alpha activity in cerebrospinal fluid increased significantly more in old rats than in young rats. Baseline levels of platelet activating factor in cerebrospinal fluid were significantly higher in old rats than in young rats, and the levels increased to a greater degree in aged rats on stimulation. Rats with the stroke risk factor of advanced age respond to lipopolysaccharide with a more exuberant production of tumor necrosis factor-alpha and platelet activating factor than young rats of the same strain. These findings are consistent with our working hypothesis that perivascular cells are capable of exaggerated signaling of endothelium through cytokines such as tumor necrosis factor-alpha in animals with stroke risk factors. The effect of such signaling might be to prepare the endothelium of the local vascular segment for thrombosis or hemorrhage in accord with the local Shwartzman reaction paradigm.

Modulation of in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. I. Inhibition by RP-3 treatment of the priming and effector phases of delayed type hypersensitivity to sheep red blood cells in rats.

Recent studies on neutrophils have revealed that these cells produce various cytokines, and may be involved in regulation of the immune response. We examined whether neutrophils are involved in delayed type hypersensitivity (DTH) to SRBC in rats by selective depletion of in vivo neutrophils using a mAb designated RP-3. When the rats had been treated with RP-3 at the time of priming with SRBC, DTH to these cells was inhibited. Furthermore, RP-3 treatment was effective in inhibiting the effector phase of the DTH response to SRBC. When spleen cells from rats that had been treated with RP-3 at the time of immunization were used for local transfer of DTH, footpad swelling was significantly less than that induced by spleen cells from the RP-3-untreated immune rats.

Modulation of in vivo immune response by selective depletion of neutrophils using a monoclonal antibody, RP-3. II. Inhibition by RP-3 treatment of mononuclear leukocyte recruitment in delayed-type hypersensitivity to sheep red blood cells in rats.

We demonstrated in our previous paper that treatment of rats with RP-3, a mAb that depletes in vivo neutrophils selectively, resulted in inhibition of both the priming and effector phases of delayed type hypersensitivity (DTH) to SRBC. In order to clarify the mechanisms of this phenomenon, we examined the effect of RP-3 treatment on mononuclear leukocyte (MNL) recruitment in DTH. When rats had been treated with RP-3 at the time of Ag priming, MNL migration, which accompanies DTH, was inhibited. The prior infiltration of neutrophils was also partially required for MNL recruitment because migration was inhibited when the immune rats were treated with RP-3 at the time of DTH elicitation.

Metabolic Fate of Zolpidem. (IV). Serum and Plasma Protein Binding of zolpidem and Its Transfer into the Blood Cells in Rats, Monkeys and Humans.

Metabolic Fate of Zolpidem. (IV). Serum and Plasma Protein Binding of zolpidem and Its Transfer into the Blood Cells in Rats, Monkeys and Humans.

Alterations of K+ transport by the alpha 1 Na(+)-K+ pump in red blood cells of the Dahl salt-sensitive rat.

We studied the kinetic properties of the Na(+)-K+ pump in rat red blood cells (RBCs) of the Dahl salt-sensitive (DS) and salt-resistant (DR) strains by measuring unidirectional ouabain-sensitive (OS) Na+ and K+ fluxes (mmol/L cell x h = FU, mean +/- SE) and varying internal (i) and external (o) Na+ and K+ concentrations. OS Na+ efflux into Nao 140 mM, Ko 5 mM was similar in both strains in fresh cells as well as for Vmax and Km for Nai. However, DS pumps have significantly lower K+ influx than DR pumps in fresh cells, thereby giving rise to a higher Na:K coupling ratio. The lower rates of K+ influx were caused by a defective activation by Nai and Nao that led to significantly lower Vmax than in DR pumps. The activation of K+ influx by Ko in the presence of 140 mM Nao had a lower Vmax and a higher affinity in DS (Vmax 2.58 +/- 0.09 FU, n = 17, Km 0.63 +/- 0.23 mM) than in DR rats (Vmax 4.7 +/- 0.3 FU, n = 16; Km 1.9 +/- 0.2 mM). However, when Nao was removed, these two kinetic parameters became similar in both strains. OS 86Rb/K efflux from fresh RBCs was significantly higher in DS than in DR rats, because the K50 from Nai inhibition was threefold higher in DS pumps. In summary, the low rates of unidirectional and net K+ influx in DS cells are caused by impaired Nai and Nao activation as well as the high values of K+ efflux are caused by low affinity for Nai inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Formation of DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) in male Fischer-344 rats

2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) is known to induce colon tumors in male Fischer-344 rats. Using 32P-postlabeling assays, we have examined PhiP-DNA adduct formation in various organs and white blood cells (WBCs) of the male Fischer-344 rat 24 h after a single oral dose of 0, 0.5, 5 or 50 mg PhIP/kg. Three PhIP-DNA adducts were detected in WBCs and in all organs, except in the liver and stomach which had only two adducts. The extent of adduct formation was dose-related, but at 0.5 mg/kg no adducts could be detected in any of the organs. At 50 mg/kg, adduct levels, expressed as relative adduct labeling values (RAL × 10 7, or adducts per 10 7 nucleotides assuming complete labeling) were highest in the large intestine (5.66), followed by WBCs (5.04), stomach (1.44), small intestine (1.32), kidney (1.16), liver (0.67) and lungs (0.52). It is concluded that orally administered PhIP forms high levels of specific DNA adducts in the large intestine, the target organ in PhIP carcinogenesis in the male Fischer-344 rat, and that the high level of adducts in WBCs indicates that significant amounts of the ultimate carcinogenic form of PhIP are present in the circulation.

Zinc uptake by blood cells of rats in zinc deficiency and inflammation.

In zinc deficiency, the function of leukocytes is impaired. However, the results of studies on the zinc concentration of blood cells in zinc deficiency are conflicting, probably in part because of technical and analytical problems. The aim of this study was to investigate, under standard conditions, the uptake of 65Zn-labeled zinc by blood cells, taken from zinc-deficient rats and from rats in which an inflammation is induced. In both conditions, the serum zinc concentration is reduced. In clinical practice, this makes it difficult to determine whether the decrease in serum zinc is the result of a real or an apparent zinc deficiency. In stress, like an inflammatory disease, the decrease of zinc reflects an apparent zinc deficiency because of redistribution of serum zinc into the liver and because of decrease in serum albumin concentration. Over 70% of the serum zinc is bound to albumin. Blood cells from zinc-deficient and control rats were isolated using a discontinuous Percoll gradient and incubated under nearly physiological conditions in a 65Zn-containing medium. A significant increase in the in vitro uptake of 65Zn-labeled zinc by the blood cells of zinc-deficient rats was seen: erythrocytes 1.3, mononuclear cells 2.0, and polymorphonuclear cells 2.6 times the control values. During inflammation, no change in 65Zn-labeled zinc uptake by erythrocytes and mononuclear cells was demonstrated after 2 d, although the serum zinc and albumin concentrations were decreased, but a small but significant increase in zinc uptake by polymorphonuclear cells was observed. This study of 65Zn uptake in vitro under standard conditions may prove of value for distinguishing in patients real zinc deficiency from apparent zinc deficiency owing to, e.g., stress, although additional experiments should be performed.

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats. Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1 alpha, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide. Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not altered significantly between the two rat strains. It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.

Glucocorticoid-induced cataract of developing chick embryo as a screening model for anticataract agents

Distinct changes of membrane lipid content could contribute to the abnormalities of ion transport that take part in the development of salt hypertension in Dahl rats. The relationships between lipid content and particular ion transport systems were studied in red blood cells (RBC) of Dahl rats kept on low- and high-salt diets for 5 weeks since weaning. Dahl salt-sensitive (SS/Jr) rats on high-salt diet had increased blood pressure, levels of plasma triacylglycerols and total plasma cholesterol compared to salt-resistant (SR/Jr) rats. Furthermore, RBC of SS/Jr rats differed from SR/Jr ones by increased content of total membrane phospholipids, but membrane cholesterol was not changed significantly. SS/Jr rats had higher RBC intracellular Na+ (Nai+) content and enhanced bumetanide-sensitive Rb+ uptake. RBC membrane content of cholesterol and phospholipids correlated positively with RBC Nai+ content, with the activity of Na+–K+ pump and Na+–K+–2Cl− cotransport and also with Rb+ leak. The content of phosphatidylserines plus phosphatidylinositols was positively associated with RBC Nai+ content, with the activity of Na+–K+ pump and Na+–K+–2Cl− cotransport and with Rb+ leak. The content of sphingomyelins was positively related to Na+–K+–2Cl− cotransport activity and negatively to ouabain-sensitive Rb+–K+ exchange. We can conclude that observed relationships between ion transport and the membrane content of cholesterol and/or sphingomyelins, which are known to regulate membrane fluidity, might participate in the pathogenesis of salt hypertension in Dahl rats.

Behavioral factors in stress-induced immunomodulation

Individual differences in the exploratory response to novelty were found to be related with the vulnerability to develop stress-induced immunological alterations. We studied the effect of exposure to inescapable shock on antibody formation against sheep red blood cells (SRBC) in rats selected according to their locomotor activity in a novel situation. Interestingly, antibody titers were only enhanced in shocked animals with the highest locomotor activity. These results emphasize the importance of taking into account individual differences for the study of the mechanisms involved in stress-induced immunomodulation, suggesting a behavioral procedure (novelty reactions) to deal with individual variability in the effects of stress on the immune system.