Effects of chronic dextromethorphan administration on the cellular immune responses in mice

We examined the chronic effect of dextromethorphan (DM) on the cellular immune responses in mice. T cell stimulator, phytohemagglutinin did not show significant effect on lymphocyte proliferation. Costimulator of T and B cell, pokeweed mitogen, and B cell stimulator, lipopolysaccharide exhibited DM-induced decreased lymphocyte proliferation. Significantly suppressed natural killer (NK) cell cytotoxicity was evidenced following 6 months DM exposure. These results suggest that chronic DM administration perturb B cell functioning and NK cell cytotoxicity. In addition, prenatal DM exposure did not potentiate the immunomodulation in postnatal effect induced by chronic DM.     

免疫器官细胞凋亡在低水平铅暴露诱导小鼠免疫损伤中的作用

目的探讨免疫器官细胞凋亡在低水平铅暴露诱导小鼠免疫损伤中的作用。方法将120只健康成年雄性昆明小鼠,分为4组,自由饮水含醋酸铅125、250、500 mg/L蒸馏水12周,对照组给予同体积的蒸馏水。染毒结束后检测小鼠胸腺、脾脏器系数及巨噬细胞吞噬功能;石墨炉原子吸收法测定血清、胸腺和脾铅含量;流式细胞术检测胸腺、脾脏细胞凋亡率。结果小鼠染铅后,高剂量组胸腺、脾脏器系数升高(P<0.05);巨噬细胞吞噬功能中、高剂量组明显下降(P<0.05或<0.01),高剂量组吞噬指数显著性降低(P<0.05);各剂量组血清、胸腺、脾脏中铅含量显著增加(P<0.05);流式细胞结果表明,各剂量染铅组胸腺细胞凋亡率均显著增加(P<0.01),高剂量组染铅组脾脏细胞凋亡率显著增加(P<0.01)。结论长期低水平铅接触可以引起胸腺和脾脏细胞过度凋亡,导致淋巴细胞结构或功能出现障碍,最终引起细胞免疫和体液免疫功能障碍。     

Aging effects on the diurnal patterns of gut microbial composition in male and female mice

Composition of the gut microbiota changes with aging and plays an important role in age-associated disease such as metabolic syndrome, cancer, and neurodegeneration. The gut microbiota composition oscillates through the day, and the disruption of their diurnal rhythm results in gut dysbiosis leading to metabolic and immune dysfunctions. It is well documented that circadian rhythm changes with age in several biological functions such as sleep, body temperature, and hormone secretion. However, it is not defined whether the diurnal pattern of gut microbial composition is affected by aging. To evaluate aging effects on the diurnal pattern of the gut microbiome, we evaluated the taxa profiles of cecal contents obtained from young and aged mice of both sexes at daytime and nighttime points by 16S rRNA gene sequencing. At the phylum level, the ratio of Firmicutes to Bacteroidetes and the relative abundances of Verrucomicrobia and Cyanobacteria were increased in aged male mice at night compared with that of young male mice. Meanwhile, the relative abundances of Sutterellaceae, Alloprevotella, Lachnospiraceae UCG-001, and Parasutterella increased in aged female mice at night compared with that of young female mice. The Lachnospiraceae NK4A136 group relative abundance increased in aged mice of both sexes but at opposite time points. These results showed the changes in diurnal patterns of gut microbial composition with aging, which varied depending on the sex of the host. We suggest that disturbed diurnal patterns of the gut microbiome can be a factor for the underlying mechanism of age-associated gut dysbiosis.     

Ouabain promotes immune responses in WEHI‐3 cells to generate leukemia mice through enhancing phagocytosis and natural killer cell activities in vivo

Ouabain, a cardiotonic steroid, was used for the treatment of heart failure and atrial fibrillation and induces cancer cell apoptosis in many human cancer cells including human leukemia cells. However, there are no reports to show the effects on immune responses in a leukemia mouse model. In this study, WEHI‐3 cell generated leukemia mice were developed and treated by oral ouabain at 0, 0.75, 1.5, and 3 mg/kg for 15 days. Results indicated that ouabain did not affect body appearance, but decreased liver and spleen weights, B‐ and T‐cell proliferation at all three doses treatment and increased CD19 cells at 3.0 mg/kg treatment, decreased CD3, CD11b, and Mac‐3 cells levels compared with positive control. Furthermore, ouabain increased the macrophage phagocytosis from peripheral blood mononuclear cell and peritoneal cavity at all three doses treatment and increased NK cell activities. Ouabain restored GOT, GPT and LDH levels in WEHI‐3 leukemia mice in vivo.     

Effects of subchronic exposure of silver nanoparticles on intestinal microbiota and gut-associated immune responses in the ileum of Sprague-Dawley rats

Abstract

Silver nanoparticles (AgNP) are widely used for their antibacterial properties. Incorporation of AgNP into food-related products and health supplements represents a potential route for oral exposure to AgNP; however, the effects of such exposure on the gastrointestinal system are mostly unknown. This study evaluated changes in the populations of intestinal-microbiota and intestinal-mucosal gene expression in Sprague-Dawley rats (both male and female) that were gavaged orally with discrete sizes of AgNP (10, 75 and 110?nm) and silver acetate. Doses of AgNP (9, 18 and 36?mg/kg body weight/day) and silver acetate (100, 200 and 400?mg/kg body weight/day) were divided and administered to rats twice daily (～10?h apart) for 13 weeks. The results indicate that AgNP prompted size- and dose-dependent changes to ileal-mucosal microbial populations, as well as, intestinal gene expression and induced an apparent shift in the gut microbiota toward greater proportions of Gram-negative bacteria. DNA-based analyses revealed that exposure to 10?nm AgNP and low-dose silver acetate caused a decrease in populations of Firmicutes phyla, along with a decrease in the Lactobacillus genus. Analysis of host gene expression demonstrated that smaller sizes and lower doses of AgNP exposure prompted the decreased expression of important immunomodulatory genes, including MUC3, TLR2, TLR4, GPR43 and FOXP3. Gender-specific effects to AgNP exposure were more prominent for the gut-associated immune responses. These results indicate that the oral exposure to AgNP alter mucosa-associated microbiota and modulate the gut-associated immune response and the overall homeostasis of the intestinal tract.     

Effects of diallyl trisulfide on induction of apoptotic death in murine leukemia WEHI‐3 cells in vitro and alterations of the immune responses in normal and leukemic mice in vivo

Diallyl trisulfide (DATS), a chemopreventive dietary constituent and extracted from garlic, has been shown to against cultured many types of human cancer cell liens but the fate of apoptosis in murine leukemia cells in vitro and immune responses in leukemic mice remain elusive. Herein, we clarified the actions of DATS on growth inhibition of murine leukemia WEHI‐3 cells in vitro and used WEHI‐3 cells to generate leukemic mice in vivo, following to investigate the effects of DATS in animal model. In in vitro study, DATS induced apoptosis of WEHI‐3 cells through the G0/G1 phase arrest and induction of caspase‐3 activation. In in vivo study DATS decreased the weight of spleen of leukemia mice but did not affect the spleen weight of normal mice. DATS promoted the immune responses such as promotions of the macrophage phagocytosis and NK cell activities in WEHI‐3 leukemic and normal mice. However, DATS only promotes NK cell activities in normal mice. DATS increases the surface markers of CD11b and Mac‐3 in leukemia mice but only promoted CD3 in normal mice. In conclusion, the present study indicates that DATS induces cell death through induction of apoptosis in mice leukemia WHEI‐3 cells. DATS also promotes immune responses in leukemia and normal mice in vivo. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1343–1353, 2015.     

Protective effects of water‐soluble low‐molecular‐weight β‐(1,3‐1,6)D‐glucan purified from Aureobasidium pullulans GM‐NH‐1A1 against UFT toxicity in mice

Objectives 5‐Fluorouracil and its derivatives are widely used in the treatment of a variety of tumours. However, their use is associated with gastrointestinal toxicity, myelotoxicity and immune toxicity. In this study, we examined the protective effects of low‐molecular‐weight β‐glucan isolated from Aureobasidium pullulans GM‐NH‐1A1 against toxicity of UFT (combination of tegafur (1‐(2‐tetrahydrofuryl)‐5‐fluorouracil) and uracil) in mice bearing colon 26 tumours. Methods UFT was administered orally at 50 mg/kg once daily for 14 days alone or with orally administered low‐molecular‐weight β‐glucan, 25, 50 and 100 mg/kg twice daily. Key findings Tumour growth was inhibited equally in all treatment groups. Onset of diarrhoea, which started on day 9 of UFT administration, was delayed by concomitant administration of the β‐glucan (50 and 100 mg/kg twice daily). Histological analysis showed that damage to small‐intestine villi by UFT was inhibited by the orally administered β‐glucan. Conclusions Oral administration of low‐molecular‐weight β‐glucan prevents gastrointestinal mucositis associated with UFT therapy without interfering with its anti‐tumour activity.     

弓形体重组质粒pcDNA_3-SAG1免疫小鼠诱导的细胞免疫应答研究

目的 :用 pc DNA3- SAG1真核表达质粒直接免疫小鼠 ,观察 DNA免疫所诱导的小鼠细胞免疫应答 ,为研制弓形虫疫苗奠定基础。方法 :大量制备重组质粒 pc DAN3- SAG1,然后将其导入 BAL B/ c小鼠体内 ,每隔 2 1d接种一次 ,一共免疫三次。用 MTT方法对脾脏的 NK细胞和其淋巴细胞的转化率进行测定 ;采用免疫荧光法对 CD4+、CD8+ 细胞进行测定。结果 :实验组 NK细胞杀伤率为 :70 .0± 3.6 4,而 pc DNA3及空白对照分别为 :48.5± 6 .0 8和 47.0± 5 .93。实验组 NK细胞活性比对照组明显增高 (P<0 .0 5 ) ,而 pc DNA3质粒及空白对照组差异无显著性 (P>0 .0 5 ) ;对 T淋巴细胞亚群 CD4+、CD8+进行动态分析 ,可见随着感染时间的延长 ,CD8+的数量逐渐上升 ,CD4+ / CD8+的比率逐渐下降 ,实验组与 pc DNA3质粒及空白对照有明显差异 (P<0 .0 5 ) ;Con A刺激小鼠淋巴细胞转化实验 ,能刺激免疫鼠及对照鼠淋巴细胞增生 ,实验组与 pc DNA3质粒及空白对照组差异无显著性 (P>0 .0 5 )。结论 :重组质粒pc DNA3- SAG1免疫 BAL B/ c小鼠可诱导一定的细胞免疫。     

Phenethyl isothiocyanate promotes immune responses in normal BALB/c mice,inhibits murine leukemia WEHI‐3 cells,and stimulates immunomodulations in vivo

Enhanced cruciferous vegetable consumption is associated with the reduction of cancer incidence as shown in epidemiological studies. Phenethyl isothiocyanate (PEITC), one of the important compounds in cruciferous vegetables, has been shown to induce apoptosis in many types of human cancer cell lines, but there is no available information addressing the effects on normal and leukemia mice in vivo. The purpose of this study is to focus on the in vivo effects of PEITC on immune responses of normal and WEHI‐3 leukemia BALB/c mice in vivo. Influences of PEITC on BALB/c mice after intraperitoneal (i.p.) injection with WEHI‐3 cells and normal mice were investigated. In normal BALB/c mice, PEITC did not affect the body weight when compared to the olive oil treated animals. Moreover, PEITC promoted phagocytosis by macrophages from peripheral blood mononuclear cells (PBMC) and peritoneal cavity, increased the levels of CD11b and Mac‐3, decreased the level of CD19 and promoted natural killer (NK) cell cytotoxic activity, but it did not alter the level of CD3. Also, PEITC enhanced T cell proliferation after concanavalin A (Con A) stimulation. Otherwise, PEITC increased the body weight, but decreased the weight of liver and spleen as compared to the olive oil‐treated WEHI‐3 leukemia mice. PEITC also increased the level of CD19, decreased the levels of CD3 and Mac‐3 rather than influence in the level of CD11b, suggesting that the differentiation of the precursor of macrophages and T cells was inhibited, but the differentiation of the precursor of B cells was promoted in leukemia mice. Furthermore, PEITC enhanced phagocytosis by monocytes and macrophages from PBMC and peritoneal cavity, and also promoted the NK cell cytotoxic activity in comparison with the group of leukemia mice. Based on these observations, the biological properties of PEITC can promote immune responses in normal and WEHI‐3 leukemia mice in vivo. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.     

Effects of escin on acute inflammation and the immune system in mice

Escin has been used extensively to treat chronic venous insufficiency, hemorrhoids, and edema resulting from cerebral ischemic damage, trauma or operation. However, no studies have looked at the anti-inflammatory properties of escin administered by intravenous injection, and it is still not clear whether escin has an effect on the immune system. This study seeks to investigate the time dependent anti-inflammatory properties of escin and its effect on the immune system. The anti-inflammatory effect of escin was observed in carrageenan-induced paw edema and acetic acid-induced capillary permeability in mice. The immunopharmacological effects of escin were evaluated by spleen index (SI), thymus index (TI), proliferative capacity of splenocytes (PS), lymphocyte count (LC), serum TNF-α levels, and phagocytic rate (PR) in mice. Escin treatment showed a significant anti-inflammatory effect, similar to that seen with dexamethasone treatment. However, the duration of the anti-inflammatory response was longer with escin treatment than with dexamethasone treatment. The results also demonstrated that escin had no significant effects on SI, TI, LC, PS, TNF-α levels, and PR. The findings suggest that escin is a potent anti-inflammatory drug with long-lasting anti-inflammatory effects and without any immunosuppressive effects.     

Modulating effects of nonselective and selective phosphodiesterase inhibitors on lymphocyte subsets and humoral immune response in mice

Phosphodiesterase (PDE) inhibitors can regulate the activity of immune cells by increasing intracellular levels of cyclic nucleotides. The aim of this study was to determine the effects of milrinone, a selective PDE3 inhibitor, sildenafil, a selective PDE5 inhibitor, and aminophylline, a nonselective PDE inhibitor, on lymphocyte subsets and humoral immune response in mice when administered in vivo. Aminophylline (20 mg/kg, i.m.), milrinone (1 mg/kg, i.m.) or sildenafil (1 mg/kg, p.o.) were administered to mice either once or five times at 24 h intervals. Some mice were immunized with a sheep red blood cell (SRBC) suspension administered i.p. either 2 h after the single dose or 2 h after the second of the five doses. In non-immunized mice treated five times with PDE inhibitors, the subsets of T lymphocytes in the thymus and T and B lymphocytes in the spleen and mesenteric lymph nodes were determined 12, 24 or 72 h after the last dose. The humoral immune response was determined on days 4, 7 and 14 after SRBC injection in SRBC-immunized mice treated with PDE inhibitors. A modulating effect of the drugs on lymphocyte subpopulations was observed. The greatest impact was observed in splenocyte subpopulations, and resulted in decreased percentages of B cells (CD19(+)) and increased percentages of T cells (CD3(+), CD4(+), CD8(+)). No effect or slight influence of the drugs on anti-SRBC hemagglutinins was observed, but the number of plaque-forming splenocytes was increased. The drugs under investigation did not show a significant immunosuppressive effect.     

The effects of perinatal/juvenile heptachlor exposure on adult immune and reproductive system function in rats.

This study was performed to determine if developmental exposure of rats to heptachlor (H) during the last half of gestation through puberty adversely affects adult functioning of the immune and reproductive systems. Time-bred pregnant female Sprague-Dawley rats were dosed by gavage with H (0, 30, 300, or 3000 microg/kg/day) from gestation day (GD) 12 to postnatal day (PND) 7, followed by direct dosing of the pups with H through PND 42. Separate groups of rats were evaluated with a battery of immune function tests, while other groups of rats were evaluated for reproductive development and function. Additional groups of rats were euthanized at the end of the dosing period for histological analyses of major organ systems. Some dams and PND 7 pups were euthanized; milk, plasma, fat and/or tissues were assayed for H and heptachlor epoxide B (HEB), a major metabolite of H. The amount of H and HEB found in milk, blood, fat, and tissues was proportional to the dose of H administered. There were no effects on the number or survival of pups born to H-exposed dams nor to pups exposed postnatally. There were no effects on the number of treated dams delivering litters or on litter size, nor were there any effects on any of the reproductive end points examined in the F(0) or F(1) rats. There were no effects of H exposure on lymphoid organ weights, splenic natural killer (NK) cell activity, and splenic lymphoproliferative (LP) responses to mitogens and allogeneic cells in a mixed lymphocyte response (MLR) assay at 8 weeks of age. H exposure did not alter delayed or contact hypersensitivity at 10 or 17 weeks of age, respectively. However, the primary IgM antibody response to sheep red blood cells (SRBCs) was suppressed in a dose-dependent manner in males, but not females, at 8 weeks of age. The percentage of B lymphocytes (OX12(+)OX19(-)) in spleen was also reduced in the high-dose males. The anti-SRBC IgM response was reduced only in males exposed to 30 microg H/kg/day in a separate group of rats 21 weeks of age. In these same rats, at 26 weeks of age, the secondary IgG antibody response to SRBCs was suppressed in all of the H-exposed males, but not females. These data indicate that perinatal exposure of male rats to H results in suppression of the primary IgM and secondary IgG anti-SRBC responses. Suppression of these antibody responses persisted for up to 20 weeks after the last exposure to H, at a total exposure of approximately 1500 microg H/kg/rat.     

Assessment of the acute toxic effects of the fungicide Ridomil plus 72 on aquatic organisms and soil micro‐organisms

The acute toxic effects of Ridomil plus 72 (Ridomil), used as a fungicide in agriculture, were studied under laboratory conditions. These effects on freshwater cladoceran (Chydorus eurynotus) and freshwater fish (Oreochromis niloticus) were determined using standard bioassay procedures. The 4 h LC₅₀ for Chydorus eurynotus was 6.9 mg/L and the 96 h LC₅₀ for Oreochromis niloticus was 1.1 mg/L. The toxicity of Ridomil to a mixed population of soil micro‐organisms was measured using oxygen uptake and growth as measured by turbidity. At short‐term exposure (48 min), Ridomil was moderately toxic to the culture at 5000 mg/L and above, based on an activity quotient (AQ) of 0.50–0.70. For longer exposure periods (up to 6 h), Ridomil was slightly toxic to the culture at 200 to 500 mg/L. At 1000 mg/L, Ridomil was moderately toxic and at 3000 mg/L and above, Ridomil was extremely toxic to soil microorganisms. The toxicity of metalaxyl (one of the two active ingredients of Ridomil) to these micro‐organisms was measured using growth as measured by the turbidity change. The average toxic endpoint (16 h IC₅₀) was 1100 mg/L. The acute toxic values of Ridomil found in these studies were much below the expected environmental concentrations resulting from normal applications of the chemical on a cocoa tree as a fungicide. ©2000 John Wiley & Sons, Inc. Environ Toxicol 15: 65–70, 2000     

Biological effects of new‐generation dialkyl phosphinate flame retardants and their hydrolysates in BALB/C mice

Aluminum methylcyclohexylphosphinate (AMHP), calcium methylcyclohexylphosphinate (CMHP), aluminum diethylphosphinate (ADEP), and aluminum methylethylphosphinate (AMEP) are organic dialkyl phosphinates (DPs) and emerging phosphorus‐based flame retardants. The broad‐spectrum DPs flame retardants occupy high‐end industrial markets, but their ecologic risk has been reported rarely. By exposing male BALB/c mice to DPs and dialkyl phosphinic acids, we studied the toxic effects of these chemicals, and measured AMHP and methylcyclohexylphosphinic acid (MHPA) in blood and feces. We found that DPs and their main hydrolysates had mild toxicity in BALB/c mice. Exposure to 10 and 50 mg/kg/d of AMEP and ADEP caused mild hepatotoxicity in mice. Toxicity of CMHP was in the liver and kidneys. Toxicity of AMHP and its hydrolysate MHPA was low and affected the liver. These data suggest that AMHP has lower toxicity than the other DPs that we tested. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1578–1586, 2017.     

维生素E对P.y17XL感染BALB/c小鼠早期Th1应答的免疫调节作用

目的探讨维生素E对致死型约氏疟原虫感染BALB/c小鼠Th1免疫应答的调节效应。方法将6～8周、雌性BALB/c小鼠经腹腔接种1×106P.yl7XL寄生的红细胞,并随机分为实验组与感染对照组,实验组于感染前10d口服给予VE预处理。流式细胞术检测感染后第0、3、5天脾Tregs的百分含量;ELISA检测脾细胞培养上清中的IFN-γ、IL-10的水平;Griess反应检测脾细胞培养上清中一氧化氮的含量。结果与正常感染组比较:补充VE组Tregs增殖明显增多;补充VE组IFN-γ和NO分泌减少,而IL-10的分泌水平增加。结论在P.yl7XL感染早期,VE预处理可显著抑制Th1免疫应答效应,从而进一步加剧P.y17XL感染BALB/c的死亡进程。     

黄芪对D-半乳糖衰老大鼠脂质过氧化及红细胞免疫功能的影响

目的 探讨黄芪对D-半乳糖衰老大鼠脂质过氧化及红细胞免疫功能的影响.方法 30只Wister大鼠分为正常对照组、D-半乳糖模型组和黄芪给药组,测定血清丙二醛(MDA)、心肌组织脂褐素(LPF)的含量、红细胞C3b受体花环率(RBC-C3bRR)、红细胞免疫复合物花环率(RBC- ICR).结果 与正常对照组相比较,D-半乳糖模型组大鼠体内血清MDA、心肌LPF含量和RBC-ICR升高,RBC-C3bRR降低(P＜0.01);而给予黄芪后,D-半乳糖模型大鼠体内血清MDA和心肌LPF含量降低,RBC-C3bRR升高、RBC-ICR降低(P＜0.01).结论 黄芪可以通过降低脂质过氧化水平,增强红细胞免疫功能而发挥抗衰老作用.     

环磷酰胺衍生物SLXM-2对小鼠脑瘤B_(22)的抗肿瘤作用及机制

目的:研究环磷酰胺衍生物SLXM-2对小鼠脑瘤B22的抗肿瘤作用及对小鼠免疫系统的影响,并探讨其抑瘤作用的分子机制。方法:采用小鼠脑瘤B22移植性肿瘤模型评价SLXM-2的抑瘤作用,测定免疫器官的脏器指数和白细胞数量;通过Western Blot检测SLXM-2对细胞周期相关蛋白表达的影响。结果:20,40 mg.kg-1 SLXM-2对小鼠脑瘤B22的抑瘤率分别为11.5%和53.9%;与阴性对照组相比,SLXM-2对小鼠免疫器官的脏器指数及白细胞数量无明显影响,可上调p53,p21,CDK7,Wee1,p-Cdc2(Tyr15),p-Cdc2(Thr 161)和CyclinB1等蛋白表达,下调CyclinE的表达,Cdc2,CDK2和Cdc25C表达水平变化不明显。结论:SLXM-2对小鼠脑瘤B22的生长有一定抑制作用,对小鼠免疫器官指数和白细胞数量没有影响;SLXM-2的抗肿瘤机制与调节p53,p21,Wee1,p-Cdc2(Tyr15)和CyclinE等蛋白表达有关。     

Effect of tributyltin (TBT) in the metabolic activity of TBT‐resistant and sensitive estuarine bacteria

The effect of tributyltin (TBT) on growth and metabolic activity of three estuarine bacteria with different TBT resistance profiles was investigated in an organic‐rich culture medium (TSB) and in phosphate buffered saline (PBS) buffer. Exposure to TBT was assessed by determining its effect on growth (OD_{600 nm} measurement), bacterial productivity (leucine incorporation), viability (CFU counts), aggregation and cell size (from Live/Dead analysis), ATP and NADH concentrations. TBT exposure resulted in decrease of bacterial density, cell size, and metabolic activity. In addition, cell aggregates were observed in the TBT‐treated cultures. TBT strongly affected bacterial cell metabolism and seemed to exert an effect on its equilibrium, interfering with cell activity. Also, TBT toxicity was lower when cells were grown in TSB than in PBS, suggesting that a nutrient‐rich growth medium can protect cells from TBT toxicity. This study contributes to our understanding of the TBT‐resistant cell behavior reflected in its physiology and metabolic activity. This information is of utmost importance for further studies of TBT bioremediation. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.     

Endothelial cationic amino acid transporter‐1 overexpression blunts the effects of oxidative stress on pressor responses to behavioural stress in mice

Observational studies indicate that psychological stress may contribute to the pathogenesis of hypertension and this may be further accentuated by factors such as endothelial dysfunction. On this basis, we aimed to determine whether oxidative stress enhances pressor responses to stressful stimuli and whether augmenting endothelial function by increasing the transport of l ‐arginine can counter the effects of oxidative stress. Telemetry probes were used to measure mean arterial pressure (MAP) in wild‐type (WT; n = 6) and endothelial cationic amino acid transporter‐1 (CAT‐1)‐overexpressing (CAT+) mice (n = 6) before and during an aversive (restraint) and non‐aversive (almond feeding) stressor. The superoxide dismutase inhibitor diethyldithiocarbamic acid (DETCA; 30 mg/kg per day; 14 days) was then administered via a minipump to induce oxidative stress. Stress responses to feeding and restraint were repeated during Days 11–12 of DETCA infusion. In WT mice, pressor responses to restraint and feeding were augmented during infusion of DETCA (35 ± 1 and 28 ± 1 mmHg, respectively) compared with respective pretreatment responses (28 ± 2 and 24 ± 1 mmHg, respectively; P ≤ 0.01). In CAT+ mice, pressor responses to feeding were blunted during DETCA (20 ± 1 mmHg) compared with the control response (23 ± 1 mmHg; P = 0.03). In these mice, pressor responses to restraint were similar before (28 ± 1 mmHg) and during (26 ± 1 mmHg) DETCA infusion (P = 0.26). We conclude that endothelial CAT‐1 overexpression can counter the ability of oxidative stress to augment pressor responses to behavioural stress.