Gender differences in vascular reactivity to endothelin-1 (1-31) in mesenteric arteries from diabetic mice

Endothelin-1 (1-31) [ET-1 (1-31)], a novel member of the ET family, comprises 31 amino acids and is derived from the selective hydrolysis of big ET-1 by chymase. Although ET-1 (1-31) reportedly exerts biological effects by direct or indirect [via its conversion to ET-1 (1-21)] mechanisms, it is unclear whether in diabetes the vascular effects of ET-1 (1-31) display gender differences. We investigated this question by exposing mesenteric artery rings to ET-1 (1-31), using arteries from mice in the early or chronic phase of diabetes. In the early stage of diabetes, the ET-1 (1-31)-induced contraction was similar between age- and sex-matched control and streptozotocin (STZ)-induced diabetic mice. In the chronic stage of diabetes, the ET-1 (1-31)-induced contraction was enhanced in diabetic female mice, but not in diabetic male mice (vs. both age-matched control and early-stage diabetic mice). This enhancement was largely prevented by Y27632 (Rho kinase inhibitor), PD98059 [inhibitor of extracellular signal related kinases 1 and 2 (ERK1/2)], or SP600125 [C-jun terminal kinase (JNK) inhibitor]. These data indicate that the ET-1 (1-31)-induced vasoconstriction in the mesenteric artery may be specifically enhanced in established diabetic female mice, and that this enhancement may be due to alterations in the activities of Rho/Rho kinase or mitogen-activated protein kinase.     

Gender differences in CMS and the effects of antidepressant venlafaxine in rats

Gender differences in susceptibility to chronic mild stress (CMS) and effects of venlafaxine in rats have been investigated in the current study. Male and female SD rats were exposed to CMS or CMS plus chronic venlafaxine administration (10 mg/kg, 21 days) in order to study depressive behavior in rats. Rats were tested in open field test and sucrose preference test to figure out gender differences in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus of rats were detected to explore the possible mechanism. The results showed that the CMS impact on behavioral parameters and corticosterone levels and response to venlafaxine were gender dependent. Female rats appeared more vulnerable in the dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive-like behavior in both gender. However, venlafaxine treated male rats exhibited better improved explore behavior and anhedonia. FKBP5 might be involved in the explanation of gender differences in CMS and venlafaxine treatment. Male and female rats respond differently to chronic stress and venlafaxine continuous treatment. This results have guiding meaning in design of trials related to stress induced depression.     

Connective tissue is involved in adult epithelial development of the small intestine during anuran metamorphosis in vitro

Summary The role of connective tissue in metamorphic changes of the small intestinal epithelium inXenopus laevis tadpoles was investigated by using organ culture techniques and electron microscopy. Tissue fragments isolated from various parts of the small intestine at stage 57 were cultivated. Larval cell death of the epithelium was induced by thyroid hormone in all fragments, whereas adult epithelial development was observed only in fragments isolated from the anterior intestinal region containing the typhlosole where most of the larval connective tissue was localized. The epithelium was then cultivated in recombination with homologous or heterologous non-epithelial components. The adult epithelium developed only in recombinants containing a thick connective tissue layer from the typhlosole. There was no regional difference in the developmental potency of the epithelium itself. In all explants where adult epithelium developed, the connective tissue increased in cell density just beneath the epithelium, which was rapidly proliferating and forming typical islets. At the same time, fibroblasts possessing well-developed rough endoplasmic reticulum differentiated close to epithelial cells and often made contact with them. These results indicate that the connective tissue originating from the typhlosole plays an important role in adult epithelial development of the anuran small intestine, probably via direct cell-to-cell contacts or some factor(s) synthesized by the fibroblasts.     

Age-related changes in the distribution and frequency of myeloid and T cell populations in the small intestine of calves

Mucosal dendritic cells (DCs) play a key role in discriminating between dietary antigens, commensal microflora and pathogens but little is known regarding age-related changes in mucosal DC populations. We analyzed lymphoid and myeloid populations within the epithelium and lamina propria (LP) of the ileum and jejunum of weaned calves (6 months old) and compared their frequency and distribution with newborn calves (3–5 weeks old). CD4, CD8 and γδ TcR T cells and CD11c^HiMHC Class II⁺ myeloid cell frequency were significantly different when comparing ileum and jejunum of weaned calves. In particular, the number of CD8 and γδ TcR T cells, and CD11c^HiCD14⁺ macrophages was significantly greater in the ileum but CD11c⁺ and CD11b⁺ myeloid cell distribution was similar throughout the mucosal epithelium of the small intestine. Furthermore, significant age-related changes were apparent when comparing the frequency and abundance of mucosal leukocyte subpopulations in newborn and weaned calves. Total mucosal leukocytes (CD45⁺) increased significantly with age in both ileum and jejunum and much of this increase was attributed to mucosal T cells (CD3⁺). In particular, CD4 T cells and NK cells increased significantly in the jejunum and CD8, and γδ TcR T cells increased significantly with age throughout the small intestine. In contrast, CD11c^HiMHC Class II⁺ myeloid cells remained numerically unchanged with age but DCs (CD13⁺, CD26⁺, CD205⁺) were enriched and macrophages (CD14⁺, CD172a⁺) were depleted in older animals. Therefore, regional differences between ileal and jejunal mucosal leukocytes changed with age and there was also a marked age-dependent change in the composition of mucosal myeloid cells. These observations have significant implications for host responses to both pathogens and commensal microflora.     

Age and segmental differences in 5-hydroxytryptamine-induced hypersecretion in the pig small intestine

5-Hydroxytryptamine is a mediator in cholera toxin-induced hypersecretion in the small intestine. Our hypothesis is that the hypersecretion induced by 5-hydroxytryptamine in the small intestine decreases with increasing age and in an aboral direction in the small intestine. In vivo, measuring accumulated fluid in ligated loops, the apparent maximal efficacy of the 5-hydroxytryptamine-induced jejunal secretion in pig neonates was 4.8±1.1 mg·mg^–1 dry loop·45 min^–1. The apparent maximal efficacy decreased by 23% and 63% in young and adult pigs, respectively, compared with neonates. In vitro, measuring changes in short-circuit current in Ussing chambers, the apparent maximal efficacy was 66.7±4.8 A·cm^–2 in neonates and was reduced by 30% and 57% in young and adult pigs, respectively. Young pigs were used in the segmental study. The apparent maximal efficacy in vivo was 3.7±0.5 mg·mg^–1 dry loop and decreased by 22% and 56% in the mid and distal small intestine, respectively. By contrast, in vitro the apparent maximal efficacy was elevated by 56% to 72.0±5.0 A·cm^–2 in the distal compared with the proximal part. In conclusion, the secretory response to 5-hydroxytryptamine in pig small intestine decreases with increasing age and in the aboral direction according to in vivo results. We suggest that the decrease in sensitivity to 5-hydroxytryptamine can explain a part of the reduced secretory response to cholera toxin with age and in the aboral direction of the small intestine.Abbreviations ASF pituitary peptide antisecretory factor - AMP cyclic adenosine monophosphate - CT cholera toxin - E _max apparent maximal efficacy - EC enterochromaffine ENS enteric nerve system - 5-HT 5-hydroxytryptamine serotonin - LT heat-labile - E. coli enterotoxin - PD electrical potential difference - R tissue resistance - SCC short-circuit current - VIP vasoactive intestinal peptide     

Close relationships between the cells of the immune system and the epithelial cells in the rat small intestine

Summary A possible contribution of the intestinal epithelium to the immune defence system was studied by electron microscopy in the rat small intestine. The cells of the immune system (CIS) such as lymphocytes, eosinophils and macrophages penetrate the basal lamina into the epithelium and make close relationships with the absorptive cells. At the points of close apposition, the two cell membranes run parallel at a regular distance of about 20 nm. On the other hand, about 5% of the intestinal absorptive cells also penetrate the basal lamina into the lamina propria via their basal protrusions and show a similar close association with CIS. The basal protrusions contain many microfilaments; this indicates that they are structures with a definite function rather than a simple hernia. These findings are discussed with respect to the transport of antigenic molecules and of intercellular communication between CIS and the intestinal epithelium.     

Gender differences in the antinociceptive effect of tramadol,alone or in combination with gabapentin,in mice

Gender difference in the antinociceptive effect of tramadol and gabapentin (alone or in combination) were investigated in mice. For investigation of acute antinociceptive effect, tramadol and gabapentin were administered to mice by intraperitoneal injection and per os, respectively, and antinociceptive activity was measured by the tail-flick test 30 min after drug administration. For investigation of the development of antinociceptive tolerance to analgesics, mice were injected with tramadol (60 mg/kg), alone or in combination with gabapentin (75 mg/kg), twice daily for seven consecutive days and the tail-flicks were tested on experimental days 1, 3, 5 and 7. Results showed there was a lower ED₅₀ value of tramadol antinociception in males than in females, indicating that females were less sensitive to the drug. Gabapentin produces a limited antinociception in both males and females. The combination of gabapentin and tramadol produced synergistic effect without gender difference. Repeated administration of tramadol produced antinociceptive tolerance in both genders. Gabapentin produced synergistic effect in tramadol-tolerant mice and repeated administration of gabapentin did not alter the synergistic effect in tramadol-tolerant mice. Because females show a higher overall prevalence of pain and less sensitivity to opioids, our finding may suggest a clinical significance of combined use of the two drugs.     

Gastrointestinal absorption and metabolism of apple polyphenols ex vivo by the pig intestinal mucosa in the Ussing chamber

Polyphenols contained in food have various positive effects on human health. The absorption and metabolism of polyphenols in the intestinal tract needs to be studied to estimate these effects. The Ussing chamber technique was used to investigate the transport behavior of apple polyphenols through pig small intestinal mucosa, which served as a model for human gastrointestinal mucosa. The identities and concentrations of polyphenols and their metabolites in the half-chambers (luminal and basolateral) within an incubation period of 4 h were determined by HPLC–MS/MS and HPLC–DAD (DAD = diode-array detection). Flux values were also measured. It was found that 5-caffeoylquinic acid and caffeic acid were absorbed and translocated to the basolateral side (1.9 and 3.7%, respectively), but other compounds, including glycosides of phloretin and quercetin, were observed without translocation. A Ussing chamber utilizing pig small intestinal mucosa is a suitable model for assessing the effect of apple polyphenols on mucosal integrity and nutrition absorption across porcine mucosa.     

Gender and genetic differences in bladder smooth muscle PPAR mRNA in a porcine model of the metabolic syndrome

The metabolic syndrome and diabetes are associated with bladder dysfunction in many people. Peroxisome proliferator-activated receptors (PPARs) may play a role in the effects of the metabolic syndrome on bladder smooth muscle (BSM). The purpose of this study was to determine if there are gender and genetic differences in PPAR levels in BSM. We measured PPAR levels using quantitative PCR in BSM from male Yucatan swine and male and female Ossabaw Island swine, which is a model for the metabolic syndrome. Male Ossabaw swine had 0.732 ± 0.111 the amount of PPAR-α mRNA as male Yucatan swine (P < 0.05), suggesting a genetic difference in PPAR-α levels. This difference may possibly contribute to the incidence of metabolic syndrome in the Ossabaw model compared to the Yucatan model. PPAR-δ mRNA was 2-fold higher in male Ossabaw swine than in female Ossabaw swine, with no significant differences in PPAR-α levels. However, PPAR-γ mRNA was 4.067 ± 0.134 times higher in female Ossabaw swine than in their male counterparts (P < 0.001). Changing the percentage of calories derived from fat did not alter any PPAR mRNA levels. Thus, PPAR-δ and PPAR-γ mRNA levels in male and female Ossabaw swine BSM are not only different, but may also result in gender differences in lipid metabolism in bladder smooth muscle. We conclude that PPAR profiles in BSM may contribute to the susceptibility of BSM to lipotoxicity in the metabolic syndrome.     

Gender difference in the relationship of performance in the handgrip and standing long jump tests to lean limb volume in young adults

Groups of young, adult males and females performed the handgrip and standing long jump tests. Their total forearm and leg volumes were calculated from a series of circumference and length measurements, and the lean volumes (bone + muscle) calculated by taking the skinfold thickness into consideration. In the handgrip, the mean female performance was 298 N compared with 496 N for the males. In the standing long jump, mean performance expressed as distance x body mass was 87.3 kg.m for females compared with 137.7 kg.m for males. These superior performances of males could simply reflect their greater muscle mass, as the mean lean volumes of female and male limbs respectively were 0.54 l and 0.89 l for forearms, and 11.82 l and 14.82 l for the two legs. However, when the performances of males and females were grouped by lean limb volume, it was found that while in both tests there were linear relationships, males and females did not share a common line. In both tests the male relationship was at a higher level than the female; therefore, for a given lean volume, the male performance was significantly superior to that of the female. The gender difference found in this study has not been seen in other studies in which the performance of skeletal muscle has been related to the cross-sectional area of the active muscles and the possible reasons for the differences are considered.     

Characterization of macrophage-like cells in the external layers of human small and large intestine

Summary In the external layers of human small and large intestine macrophage-like cells were characterized by immunohistochemical, histochemical and electronmicroscopical methods. Using immunohistochemistry and a number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of macrophages were evaluated. In all locations macrophage-like cells were identified with antibody EBM11, which recognizes CD68 antigen, C3bi which recognizes CD11b, and partly with an antibody which recognizes protein 150,95 (CD11c). Macrophage-like cells in the external muscle layer were HLA-DR-positive (expressing the MHC class-II antigen), in contrast to macrophage-like cells in the subserosa and submucosa. Macrophage-like cells in the external muscle layer were mostly acid phosphatase-negative, and at the electron-microscopic level they were found to have features of macrophages: primary lysosomes, coated vesicles and pits. However, very few secondary lysosomes were present. Birbeck granules were not observed. It is concluded that in the external muscle layer of human small and large intestine numerous macrophages of a special type are present. It is discussed whether this cell type plays a role in gastrointestinal motility and/or has an immunological function.     

the influence of lentinus edodes (shiitake mushroom) preparations on bacteriological and morphological aspects of the small intestine in piglets

Among substances intended to replace growth promoting antibiotics in pig nutrition, non-digestible oligosaccharides or polysaccharides could be potential alternative compounds. Therefore, the influence of β-1,3-1,6 glucans on bacteriological, biochemical and morphological aspects of the small intestine in weaned piglets was investigated. As sources of β-glucans, Lentinan (extract of Lentinus edodes mycelium) or dried L. edodes mycelium were added to the diet. Four homogenous groups of 5 newly weaned piglets (4 weeks of age) received one of four diets: control diet (C), C supplemented with Avilamycin (50?mg/kg, positive control), C supplemented with 0.1% of Lentinan and C supplemented with 5% of dried L. edodes mycelium powder. A first group of 10 piglets was euthanized after 11 days and the remaining 10 on day 12 of the experiment. The gastrointestinal tract was divided in segments and samples taken from digesta (stomach, proximal and distal jejunum, caecum), mucosal scrapings (jejunum) and ring shaped tissue samples (1?cm) of proximal and distal jejunum. Bacterial counts were made with digesta and mucosal samples, and short-chain fatty acids (SCFA), lactic acid and ammonia concentrations were determined. Tissue samples of both jejunal sites were embedded in paraffin wax for morphometrical (villus length, crypt depth) and histological observations (numbers of intraepithelial lymphocytes (IEL), goblet cells, apoptotic enterocytes on villi, mitotic cells in crypts). Only the diet containing 5% of dried L. edodes consistently resulted in lower viable counts (ca. 1?–?2 log₁₀ CFU) of total bacteria, E. coli, streptococci and lactic acid bacteria, and luminal and mucosal effects agreed very well. With this diet, acetate and butyrate concentrations in the distal jejunum were doubled, which is favourable in view of the trophic effect on enterocytes and colonocytes. Villus length (V) was increased with both diets containing β-glucans while crypt depth (C) was not altered, but V/C was higher. IEL counts were decreased by both diets although bacterial numbers, which is only one parameter of bacterial load, were only diminished with the L. edodes feed. The three supplemented feeds lowered the number of apoptotic enterocytes on the villi, but these numbers were very low (control diet?:?44 cells per 100 villi), making clear interpretation difficult. The mitotic index was slightly lower with the L. edodes feed, although not statistically significant. Decreased viable counts observed with the latter diet is a favourable effect as it is accepted that a lower bacterial load causes lower turnover rates of the intestinal epithelial cells, while there is also less competition for specific substrates. A higher V/C ratio, a smaller number of IEL in the epithelium and a lower apoptotic index also indicate slower turnover rate of the mucosa when Lentinan and L. edodes diets were fed. The inconsistent effects observed with Lentinan were probably due to the low amount added to the diet. It should be taken into account that the influence of L. edodes mycelium powder was more likely due to the presence of antibacterial compounds (eg. lenthionine, lentinamycin, terpenoids, polyphenols), rather than to an immunostimulating action of β-glucans with increased release of IgA onto the mucosa surface.     

热应激对小鼠器官指数、小肠损伤及胃HSP70 mRNA表达的影响

目的探讨热应激对小鼠器官指数、小肠形态、胃黏膜HSP70 mRNA表达量及糖代谢相关激素的影响。方法采用单因子实验设计,将年龄和体重相近的18只KM小鼠随机分为对照组和热应激组,分别测定心、肝、脾、肺、肾重量,小鼠胃黏膜HSP70 mRNA表达量、血浆中胰岛素和胰高血糖素浓度以及十二指肠和空肠的绒毛高度、隐窝深度,并对肝脏、十二指肠和空肠进行病理组织学检查。结果与结论热应激对小鼠器官指数无影响,可显著提高小鼠胃黏膜HSP70 mRNA表达量,降低血浆中胰岛素的含量,并造成小鼠肝脏、十二指肠和空肠严重损伤。     

The spatial and temporal concentrations of choline in the lumen contents of the small intestine of uninfected and Hymenolepis diminuta infected rats

The spatial and temporal concentrations of free choline in the lumen of the small intestine of the uninfected and Hymenolepis diminuta-infected rat were investigated. In the unfed infected or uninfected rat, the choline concentrations ranged from 500 μM in the duodenum to 20 μM in the posterior ileum, with some segments in infected rats containing significantly higher choline levels than in uninfected rats. Following feeding, choline levels were significantly elevated to approximately 3 mM by 6 h, although these concentrations fell rapidly in transit down the intestine. By 12 h the choline levels were similar to those in the unfed rat. An initial small shift in the worm biomass toward the duodenum after feeding was followed by a redistribution of biomass along the length of the small intestine. The worm biomass, however, had little or no effect on the choline levels. The high concentrations of free choline observed in the anterior regions of the intestine are postulated to be predominantly determined by nutritional intake while the concentrations in the posterior region may in part be determined by blood choline levels. The high levels of choline indicate that choline is not limiting to support growth of the worms.     

The spatial and temporal concentrations of choline in the lumen contents of the small intestine of uninfected and Hymenolepis diminuta infected rats

The spatial and temporal concentrations of free choline in the lumen of the small intestine of the uninfected and Hymenolepis diminuta-infected rat were investigated. In the unfed infected or uninfected rat, the choline concentrations ranged from approximately 500 microM in the duodenum to approximately 20 microM in the posterior ileum, with some segments in infected rats containing significantly higher choline levels than in uninfected rats. Following feeding, choline levels were significantly elevated to approximately 3 mM by 6 h, although these concentrations fell rapidly in transit down the intestine. By 12 h the choline levels were similar to those in the unfed rat. An initial small shift in the worm biomass toward the duodenum after feeding was followed by a redistribution of biomass along the length of the small intestine. The worm biomass, however, had little or no effect on the choline levels. The high concentrations of free choline observed in the anterior regions of the intestine are postulated to be predominantly determined by nutritional intake while the concentrations in the posterior region may in part be determined by blood choline levels. The high levels of choline indicate that choline is not limiting to support the growth of the worms.     

Isobaric labeling-based quantitative proteomics of FACS-purified immune cells and epithelial cells from the intestine of Crohn's disease patients reveals proteome changes of potential importance in disease pathogenesis

Crohn's disease (CD) is a chronic condition characterized by recurrent flares of inflammation in the gastrointestinal tract. Disease etiology is poorly understood and is characterized by dysregulated immune activation that progressively destroys intestinal tissue. Key cellular compartments in disease pathogenesis are the intestinal epithelial layer and its underlying lamina propria. While the epithelium contains predominantly epithelial cells, the lamina propria is enriched in immune cells. Deciphering proteome changes in different cell populations is important to understand CD pathogenesis. Here, using isobaric labeling-based quantitative proteomics, we perform an exploratory study to analyze in-depth proteome changes in epithelial cells, immune cells and stromal cells in CD patients compared to controls using cells purified by FACS. Our study revealed increased proteins associated with neutrophil degranulation and mitochondrial metabolism in immune cells of CD intestinal mucosa. We also found upregulation of proteins involved in glycosylation and secretory pathways in epithelial cells of CD patients, while proteins involved in mitochondrial metabolism were reduced. The distinct alterations in protein levels in immune- versus epithelial cells underscores the utility of proteome analysis of defined cell types. Moreover, our workflow allowing concomitant assessment of cell-type specific changes on an individual basis enables deeper insight into disease pathogenesis.     

Distribution of intrinsic nerve cell bodies and axons which take up aromatic amines and their precursors in the small intestine of the guinea-pig

Summary The sites of uptake, decarboxylation and retention of 1-dopa and the uptake and retention of dopamine and 6-hydroxytryptamine in the small intestine of the guinea-pig have been localised histochemically with a fluorescence technique for arylethylamines. In segments of ileum from untreated guinea-pigs only noradrenergic axons are fluorescent; these axons were eliminated by surgical denervation (crushing nerves running to the intestine through the mesentery) or by chemical denervation with 6-hydroxydopamine. In denervated segments of ileum, cell bodies and processes of intrinsic neurons become fluorescent after the injection of 1-dopa, dopamine or 6-hydroxytryptamine and the inhibition of monoamine oxidase, as do cells of Brunner's glands and Paneth cells. About 11% of the nerve cell bodies in the submucous plexus and 0.4% of those in the myenteric plexus become fluorescent. Varicose intrinsic axons which take up amines are found amongst the nerve cell bodies of the myenteric and submucous plexuses. They also ramify in the principal connections of the plexuses, in the tertiary strands of the myenteric plexus, in the deep muscular plexus and contribute sparse supplies of axons to arterioles in the submucosa and to the lamina propria of the mucosa. The axons are resistant to the degenerative actions of 6-hydroxydopamine.It is suggested that the intrinsic amine handling axons are more likely to utilise an indolamine related to 5-hydroxytryptamine than they are to utilise a catecholamine as a neurotransmitter.     

Analysis of the morphology and distribution of argentaffin, argyrophil and insulin-immunoreactive endocrine cells in the small intestine of the adult opossum Didelphis aurita (Wied-Neuwied, 1826)

The aim of this study was to identify and quantify the argyrophil, argentaffin and insulin-immunoreactive cells (IIC) in the small intestine of the opossum Didelphis aurita. Seven adult male specimens of opossums were investigated. The animals were captured, and their blood insulin levels were determined. After euthanasia, fragments of the small intestine were processed for light microscopy and transmission electron microscopy, and submitted to histochemistry and immunohistochemistry for identification of argyrophil and argentaffin endocrine cells, and IIC. Argyrophil and argentaffin cells were identified in the intestinal villi and Liberkühn crypts, whereas IIC were present exclusively in the crypts. Ultrastructure of the IIC revealed cytoplasmic granules of different sizes and electron densities. The numbers of IIC per mm² in the duodenum and jejunum were higher than in the ileum (p < 0.05). The animals had low levels of blood insulin (2.8 ± 0.78 μIU/ml). There was no correlation between insulin levels and the number of IIC in the small intestine. The IIC presented secretory granules, elongated and variable morphology. It is believed that insulin secretion by the IIC may influence the proliferation of cells in the Liberkühn crypts, and local glucose homeostasis, primarily in animals with low serum insulin levels, such as the opossum.     

Effects of nitric oxide in 5-hydroxytryptamine-, cholera toxin-, enterotoxigenic Escherichia coli- and Salmonella Typhimurium-induced secretion in the porcine small intestine

The effects of nitric oxide (NO) in the secretory response to the endogenous secretagogue 5-hydroxytryptamine (5-HT), the enterotoxins heat-labile enterotoxigenic Escherichia coli (ETEC) toxin (LT) and cholera toxin (CT), and various cultures of ETEC and Salmonella serotype Typhimurium in the porcine small intestine (Sus scrofa) were investigated. In anaesthetized pigs, jejunal tied-off loops were instilled with 5-HT, LT, CT, various cultures of ETEC or S. Typhimurium. Pigs were given intravenously isotonic saline or isotonic saline containing the NO synthase inhibitor, N^ω-nitro-l-arginine methyl ester (L-NAME). L-NAME significantly induced an increased fluid accumulation in loops induced by 5-HT, ETEC and stn-mutated S. Typhimurium. Fluid accumulation in loops instilled with wild-type S. Typhimurium was increased by L-NAME, although not significantly, while there was no effect on fluid accumulation induced by an invH-mutated isogenic strain. No significant effect of L-NAME was observed on the fluid accumulation induced by the purified enterotoxins LT and CT. The results also demonstrated a relatively large difference in the ability to induce fluid accumulation between the bacteria strains. Diastolic, systolic and mean blood pressures were significantly increased and the body temperature was significantly decreased in groups of pigs treated with L-NAME. In conclusion, the results suggest that NO has a proabsorptive effect in the intact porcine jejunum and is involved in the systemic vascular tone.