nitroarginine and Acute-Disease

Psychological stress can suppress baroreflex function, but the mechanism has not been fully elucidated. Nitric oxide in the brain and in the adrenal cortex, as well as plasma glucocorticoids, increases during stress and has been shown to suppress reflex gain in unstressed animals. Therefore, the purpose of this study was to test the hypothesis that stress, caused by exposure to a novel environment, decreases baroreflex gain in rabbits through the actions of nitric oxide to increase corticosterone release. Baroreflex control of heart rate and plasma corticosterone levels was quantified before and after blockade of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 20 mg/kg iv) in conscious rabbits exposed to a novel environment and in the same rabbits once they had been conditioned to the environment. Stress significantly reduced baroreflex gain from -23.4 +/- 2 to -12.2 +/- 1.6 beats x min(-1) x mmHg(-1) (P < 0.05) and increased plasma corticosterone levels from 5.4 +/- 0.7 to 15.5 +/- 5.0 ng/ml (P < 0.05). NOS blockade increased gain in stressed animals (to -27.2 +/- 5.4 beats x min(-1) x mmHg(-1), P < 0.05) but did not alter gain in unstressed rabbits (-26.8 +/- 4.9 beats x min(-1) x mmHg(-1)) such that gain was equalized between the two states. NOS blockade increased plasma corticosterone levels in unstressed animals (to 14.3 +/- 2.1 ng/ml, P < 0.05) but failed to significantly alter levels in stressed rabbits (14.0 +/- 3.9 ng/ml). In conclusion, psychological stress may act via nitric oxide, independently of increases in corticosterone, to decrease baroreflex gain.

Topics: Acute Disease; Animals; Baroreflex; Blood Pressure; Corticosterone; Enzyme Inhibitors; Female; Heart Rate; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rabbits; Stress, Psychological

To identify a possible role for nitric oxide (NO) in acute hypoxic tolerance (HT) we measured hypoxic survival time (HST), effect of hypoxic conditioning (HC), and survival following hypoxic conditioning while blocking or mimicking the action of nitric oxide synthase (NOS). To inhibit NOS, CD-1 mice were given supplemental endogenous NOS inhibitor asymmetrical dimethylarginine (ADMA) or a synthetic NOS inhibitor N(omega)-nitro-L-arginine (L-NNA), both of which nonselectively inhibit three of the isoforms of NOS [inducible (iNOS), neuronal (nNOS), and endothelial NOS (eNOS)]. ADMA (10 mg/kg i.p.) or saline vehicle was given 5 min before HST testing. L-NNA was given orally at 1 g/l in drinking water with tap water as the control for 48 h before testing. Both ADMA and L-NNA significantly increased HST and augmented the HC effect on HST. Neither the nNOS selective inhibitor 7-nitroindazole (7-NI) nor the iNOS selective inhibitor N-{[3-(aminomethyl)phenyl]methyl}-enthanimidamide (1400W) had a statistically significant effect on HST or HT. The NO donor, 3-morpholinosydnoeimine, when given alone did not significantly decrease HT, but it did mitigate the increased HT effect of L-NNA. These data confirm that acute hypoxic conditioning increases HT and that NOS inhibition by endogenous (ADMA) and a synthetic NOS inhibitor (L-NNA) further increases HT, whereas iNOS and nNOS inhibition does not, suggesting that it is the inhibition of eNOS that mediates enhancement of HT.

Topics: Acute Disease; Animals; Arginine; Endothelium, Vascular; Enzyme Inhibitors; Hypoxia; Imines; Indazoles; Male; Mice; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitroarginine; Time Factors

Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis (AP). The aim of the study was to investigate an influence of L-arginine (nitric oxide substrate) and N(G)-nitro-L-arginine (L-NNA, nitric oxide synthase inhibitor) on organ microcirculation in experimental acute pancreatitis induced by four consecutive intraperitoneal cerulein injections (15 microg/kg/h). The microcirculation of pancreas, liver, kidney, stomach, colon and skeletal muscle was measured by laser Doppler flowmeter. Serum interleukin 6 and hematocrit levels were analyzed. AP resulted in a significant drop of microperfusion in all examined organ. L-arginine administration (2 x 100 mg/kg) improved the microcirculation in the pancreas, liver, kidney, colon and skeletal muscle, and lowered hematocrit levels. L-NNA treatment (2 x 25 mg/kg) caused aggravation of edematous AP to the necrotizing situation, and increased IL-6 and hematocrit levels. A further reduction of blood perfusion was noted in the stomach only. It is concluded that L-arginine administration has a positive influence on organ microcirculatory disturbances accompanying experimental cerulein-induced AP. NO inhibition aggravates the course of pancreatitis.

Topics: Acute Disease; Animals; Arginine; Ceruletide; Enzyme Inhibitors; Interleukin-6; Male; Microcirculation; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regional Blood Flow

Ghrelin, identified in the gastric mucosa, has been involved in the control of food intake and growth hormone (GH) release, but whether this hormone influences the gastric secretion and gastric mucosal integrity has been little elucidated. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without suppression of nitric oxide (NO)-synthase or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by the H2-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. In addition, the gastric mucosal expression of mRNA for CGRP, the most potent neuropeptide released from the sensory afferent nerves, was analyzed in rats exposed to WRS with or without ghrelin pre-treatment. Ghrelin (5-80 microg/kg i.p. or 0.6-5 microg/kg i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS. This protective effect was accompanied by a significant rise in the gastric mucosal blood flow (GBF), luminal NO concentration and plasma ghrelin and gastrin levels. Ghrelin-induced protection was abolished by vagotomy and significantly attenuated by L-NNA and deactivation of afferent nerves with neurotoxic dose of capsaicin. The signal for CGRP mRNA was significantly increased in gastric mucosa exposed to WRS as compared to that in the intact gastric mucosa and this was further enhanced in animals treated with ghrelin. We conclude that central and peripheral ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol or WRS, and these effects depend upon vagal activity and hyperemia mediated by the NOS-NO system and CGRP released from sensory afferent nerves.

Topics: Acute Disease; Animals; Calcitonin Gene-Related Peptide; Capsaicin; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ethanol; Gastric Acid; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Gene Expression; Ghrelin; Immersion; Injections, Intraperitoneal; Injections, Intraventricular; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Peptide Hormones; Rats; Rats, Wistar; RNA, Messenger; Stress, Physiological; Vagotomy; Water

The aims of this study were: 1) to obtain an experimental model reproducing the characteristics of chronicity and spontaneous relapses found in inflammatory bowel disease (IBD) and 2) to correlate these changes with intestinal motility and bacteria translocation. For this purpose, two groups of Sprague-Dawley rats were used: a treated group that received two subcutaneous injections of indomethacin (7.5 mg/kg) 48 h apart and a control group that received saline. Blood leukocytes, TNF, and fecal parameters were monitored for 90 days after treatment. In treated rats, a cyclic oscillation of blood leukocytes and TNF concomitant with an inverse correlation of fecal output was observed. Treated rats were then selected either during their highest or lowest blood leukocyte values for motor activity and microbiological evaluation. Controls were obtained in age-matched rats. Rats with high leukocyte levels showed a decrease of motor activity. In contrast, animals with low leukocyte levels presented hypermotility. Bacterial overgrowth accompanied by bacterial translocation was found in the group with high leukocytes, whereas no differences were observed between the control and indomethacin groups during the lowest leukocyte phase. We obtained a model of IBD characterized by a chronic cyclic oscillation of intestinal motility, flora, and inflammatory blood parameters. During the high-leukocyte stage, motor activity decrease is related to bacterial translocation. This phase is followed by a reactive one characterized by hypermotility associated with a decrease in both bacterial growth and leukocytes. However, as in IBD, this reaction seems unable to prevent a return to relapse.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bacteria; Bacterial Infections; Bacterial Translocation; Cholecystokinin; Chronic Disease; Enteritis; Enzyme Inhibitors; Gastrointestinal Motility; Indomethacin; Injections, Subcutaneous; Intestinal Diseases; Leukocyte Count; Male; Nitroarginine; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

The effect of inhibiting nitric oxide (NO) synthase (NOS) or enhancing NO on the course of acute pancreatitis (AP) is controversial, in part because three NOS isoforms exist: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). We investigated whether inhibition or selective gene deletion of NOS isoforms modified the initiation phase of caerulein-induced AP in mice and explored whether this affected pancreatic microvascular blood flow (PMBF). We investigated the effects of nonspecific NOS inhibition with N(omega)-nitro-l-arginine (l-NNA; 10 mg/kg ip) or targeted deletion of eNOS, nNOS, or iNOS genes on the initiation phase of caerulein-induced AP in mice using in vivo and in vitro models. Western blot analysis was performed to assess eNOS phosphorylation status, an indicator of enzyme activity, and microsphere studies were used to measure PMBF. l-NNA and eNOS deletion, but not nNOS or iNOS deletion, increased pancreatic trypsin activity and serum lipase during the initiation phase of in vivo caerulein-induced AP. l-NNA and eNOS did not affect trypsin activity in caerulein-hyperstimulated isolated acini, suggesting that nonacinar events mediate the effect of NOS blockade in vivo. The initiation phase of AP in wild-type mice was associated with eNOS Thr(495) residue dephosphorylation, which accompanies eNOS activation, and a 178% increase in PMBF; these effects were absent in eNOS-deleted mice. Thus eNOS is the main isoform influencing the initiation of caerulein-induced AP. eNOS-derived NO exerts a protective effect through actions on nonacinar cell types, most likely endothelial cells, to produce greater PMBF.

Topics: Acute Disease; Animals; Ceruletide; Cytoprotection; Enzyme Inhibitors; Mice; Mice, Inbred C57BL; Mice, Knockout; Microcirculation; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitroarginine; Pancreas; Pancreatitis; Phosphorylation; Regional Blood Flow; Trypsin

In experiments on the closed-chest dogs it was shown that NOS inhibition resulted in the significant alterations of hemodynamic indices (coronary and peripheral vascular resistance, cardiac output and heart rate) under local myocardial ischemia/reperfusion in comparison with control experiments. At the first time it was shown that NOS inhibition activated the autophagic destruction of cardiomyocytes in the ischemic myocardium and could reduce an area of functionally active myocardium. L-arginine administration attenuated cardio- and hemodynamic disturbances, that substantially improved the course of ischemia/reperfusion, diminished the ultrastructural changes in myocardium and prevented development of autophagic programmed cell death.

Topics: Acute Disease; Animals; Arginine; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Dogs; Enzyme Inhibitors; Male; Myocardial Reperfusion Injury; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine

The effects of acute hyperthyroidism on the vasorelaxing responses to isoprenaline and acetylcholine were investigated in isolated rat renal and femoral arteries. In the renal artery, isoprenaline- and acetylcholine-induced relaxations were significantly greater in hyperthyroid rats than in control rats. In the femoral artery, only the acetylcholine-induced relaxation was significantly greater in hyperthyroid rats than in control rats. In the renal artery, NG-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide (NO) synthase, reduced isoprenaline- and acetylcholine-induced relaxations in both hyperthyroid and control rats and the isoprenaline-induced relaxation was still greater in hyperthyroid rats than in control rats, but no difference in the acetylcholine-induced relaxation was seen between the two groups of rats since L-NOARG almost abolished the acetylcholine-induced relaxation. In the femoral artery, L-NOAGR reduced the isoprenaline-induced relaxation in control rats but not in hyperthyroid rats, while it almost abolished the acetylcholine-induced relaxation in both groups of rats. 17-Octadecynoic acid (17-ODYA), a cytochrome P-450 monooxygenase inhibitor, reduced the isoprenaline-induced relaxation in renal and femoral arteries from hyperthyroid and control rats, but it did not change the acetylcholine-induced relaxation in both arteries. These results indicate that acute hyperthyroidism significantly enhances beta-adrenoceptor-mediated relaxation of the renal artery and muscarinic receptor-mediated relaxation of both renal and femoral arteries, suggesting that these effects may be due to an alteration in the NO and cytochrome P-450 systems of the artery.

Topics: Acetylcholine; Acute Disease; Animals; Cyclooxygenase Inhibitors; Fatty Acids, Unsaturated; Femoral Artery; Heart Rate; Hyperthyroidism; Indomethacin; Isoproterenol; Japan; Male; Muscle, Smooth, Vascular; Nitroarginine; Nitroprusside; Organ Size; Rats; Rats, Wistar; Receptors, Adrenergic; Receptors, Muscarinic; Renal Artery; Thyroxine; Vasodilation

Diabetes and nitric oxide synthase (NOS) inhibition both exacerbate mesenteric ischemia/ reperfusion injury. Heat shock protein 72 (HSP-72) protects against KDa ischemia/reperfusion damage in vivo. The effect of diabetes on HSP-72 expression in vivo is unknown. The aim of this study was to determine the effects of diabetes and NOS inhibition on HSP-72 induction in vivo. Rats were assigned to four groups: control (C), streptozotocin-induced diabetic (D), acute hyperglycemia (A), and L-N(omega)-nitro-L-arginine treated (L). Rats were subjected to hyperthermia and allowed to recover for 4 hours. Intestine and liver samples from heated (H) and nonheated (NH) rats were analyzed for HSP-72 by Western blot. HSP-72 levels were increased significantly in CH compared to CNH rats. No deaths occurred in CH rats; however, death rates were significant in AH, DH, and LH rats. DH rats died earlier than LH and AH rats. HSP-72 in liver and intestine was reduced significantly in LH rats. When compared with CH rats the surviving AH and DH rats exhibited similar HSP-72 levels in the liver. Diabetes, acute hyperglycemia, and L-N(omega)-nitro-L-arginine treatment lower heat stress tolerance. NOS is required for HSP-72 expression, but not survival. Diabetics who survive heat stress moderately express HSP-72. Characterization of altered thermotolerance and HSP-72 may provide mechanisms for the deranged diabetic stress response.

Topics: Acute Disease; Animals; Blotting, Western; Diabetes Mellitus, Experimental; Enzyme Inhibitors; Heat-Shock Proteins; Hot Temperature; HSP72 Heat-Shock Proteins; Hyperglycemia; Intestinal Mucosa; Liver; Male; Nitric Oxide Synthase; Nitroarginine; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stress, Physiological

The aim of this study was to investigate coronary vascular responses, particularly NO-dependent, in the non-ischemic miocardium during local acute myocardial ischemia/reperfusion. The experiments were performed on the dogs with closed chest. Occlusion of a branch of the coronary artery resulted in a dilatation of the coronary vessels within the intact part of the myocardium. Neither inhibition of prostanoid production and KATP-channels, nor administration of atropine sulfate and dissection of the vagus nerve altered coronary dilatation within the non-ischemic myocardium. Whereas inhibition of NOS by L-NNA (50 mg/kg) completely changed it after coronary occlusion, furthermore coronary resistance temporally increased. Thus, the most reliable mechanism of that response was NO-dependent.

Topics: Acute Disease; Animals; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Dogs; Electrocardiography; Myocardial Reperfusion Injury; Myocardium; Nitric Oxide; Nitroarginine; Vasodilation

To investigate whether the retina of the rat exerts a vasodilatory influence by the release of a relaxing factor and to characterize the retinal relaxing factor (RRF).. The relaxing influence of the rat retina was investigated by placing the retina in close proximity with a precontracted isolated rat carotid artery ring segment, mounted for isometric tension measurements.. Application of rat retina relaxed the artery in a reliable and reproducible way. The nitric oxide (NO)-synthase inhibitor N(omega)-nitro-L-arginine (L-NA), the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and the removal of the endothelium of the artery all failed to affect the RRF response. The RRF response was not decreased; in contrast, it increased after treatment with a cyclooxygenase (COX) inhibitor (indomethacin or sodium diclofenac). Acute hypoxia largely enhanced retina-induced relaxation. Several potential mediators of hypoxia-induced vasodilation were excluded as candidates for the RRF or for mediating the enhanced response to RRF in hypoxia. Inhibition of the plasma membrane Ca(2+)-adenosine triphosphatase (ATPase) with vanadate significantly affected the RRF response.. The release of an as yet unidentified relaxing factor(s) from the rat retina was demonstrated. Acute hypoxia profoundly enhances the RRF response. None of the known mediators of hypoxia-induced vasodilation nor NO, prostanoids, or endothelial factors mediate the RRF response. Activation of the plasma membrane Ca(2+)-ATPase seems to be involved in the RRF response.

Topics: Acute Disease; Animals; Calcium-Transporting ATPases; Carotid Arteries; Cyclooxygenase Inhibitors; Diclofenac; Endothelium, Vascular; Enzyme Inhibitors; Female; Guanylate Cyclase; Hypoxia; In Vitro Techniques; Indomethacin; Isometric Contraction; Nitroarginine; Oxadiazoles; Quinoxalines; Rats; Rats, Wistar; Retina; Sarcoplasmic Reticulum; Thapsigargin; Vasodilation; Vasodilator Agents

Vascular endothelial growth factor, a specific endothelial mitogen, plays an important role in myocardial angiogenesis. Previous work has demonstrated increased expression of vascular endothelial growth factor and its receptors in a rat myocardial infarction model, as well as in a pig model of chronic ischemia. The expression of vascular endothelial growth factor and other growth factors after acute myocardial ischemia in patients has not been examined. In this study we examined the expression of vascular endothelial growth factor and its receptors and the responsiveness of human atrial microvessels to vascular endothelial growth factor before and after acute ischemia.. Paired specimens of human atrial tissue were harvested before and after atrial devascularization (ligation) in 16 patients undergoing coronary bypass operations.. The messenger RNA (reverse transcriptase-polymerase chain reaction) level of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 were increased by 22.2% +/- 4.2% and 30.7% +/- 7.6%, respectively (P <.05), in the ischemic specimens as compared with the control specimens. Protein expression (Western blotting) of vascular endothelial growth factor and that of vascular endothelial growth factor receptor 1 also were increased significantly by 71.7% +/- 27.8% and 68.2% +/- 27.6%, respectively (P <.05). However, both RNA and protein expressions of another vascular endothelial growth factor receptor, vascular endothelial growth factor receptor 2, and fibroblast growth factor and fibroblast growth factor receptor 1 were unchanged. Reactivity of precontracted atrial vessels was examined with video microscopy. Vascular endothelial growth factor-induced (33.9% +/- 2.4% vs 18.3% +/- 2.8% in control and ischemic vessels, respectively; P <.05), fibroblast growth factor-induced (31.6% +/- 3.2% vs 15.8% +/- 4.1%, P <.05), and substance P-induced (84.5% +/- 3.7% vs 54.3% +/- 9.0%, P <.05) microvascular relaxations were decreased in ischemic samples and in the presence of N (G)nitro-L -arginine, whereas responses to sodium nitroprusside were unchanged (90.9% +/- 2.2% vs 91.2% +/- 2.0%).. This study suggests that acute myocardial ischemia in patients results in increased expression of vascular endothelial growth factor but not fibroblast growth factor and that the functional activity of vascular endothelial growth factor receptors and that of other growth factors may be impaired.

Topics: Acute Disease; Biomarkers; Blotting, Western; Coronary Artery Bypass; Coronary Circulation; Coronary Vessels; DNA Probes; Endothelial Growth Factors; Enzyme Inhibitors; Female; Gene Expression; Heart Atria; Humans; Lymphokines; Male; Middle Aged; Myocardial Ischemia; Nitroarginine; Nitroprusside; Prognosis; Protein Isoforms; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Fibroblast Growth Factor; Receptors, Growth Factor; Receptors, Mitogen; Receptors, Vascular Endothelial Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Substance P; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vasodilation; Vasodilator Agents

Prostaglandins (PG), the products of arachidonate metabolism through cyclooxygenase (COX) pathway, protect the pancreas from the acute damage. The existence of two isoforms of COX was documented including: COX-1, present in normal tissues and COX-2, expressed at the site of inflammation, such as induced by bacterial lipopolysaccharide (LPS). Pretreatment with low dose of LPS and activation of nitric oxide (NO) synthase (NOS) has been shown to prevent the injury caused by caerulein-induced pancreatitis (CIP) in the rat. The aim of this study was to investigate the role of COX-1 and COX-2 in the LPS-induced protection of the pancreas against CIP and the involvement of NOS in the activation of COX-PG system in the rats with CIP. CIP was produced by subcutaneous (s.c.) infusion of caerulein (5 microg/kg-h for 5 h) to the conscious rats. Protective dose of LPS, from Escherichia coli, (1 mg/kg) was given intraperitoneally (i.p.) 15 min prior to the start of CIP. Nonselective inhibitor of COX; indomethacin (5 or 10 mg/kg), selective inhibitor of COX-1: resveratrol, or a highly selective inhibitors of COX-2: rofecoxib or NS-398 (2 or 10 mg/kg) were injected i.p. 15 min prior to the administration of LPS. COX-1 or COX-2 mRNA was determined by reverse transcription-polimerase chain reaction (RT-PCR) in the pancreatic tissue. Pancreatic blood flow (PBF) was measured by a laser Doppler flowmetry. PGE2 content in the pancreas was measured by radioimmunoassay. CIP was manifested by an increase of pancreatic weight and plasma amylase activity (by 500% and 700%, respectively) and it was confirmed by histological examination. CIP slightly increased pancreatic PGE2 generation (by 12%) and diminished PBF (by about 40%). LPS (1 mg/kg i.p.), given prior to the start of CIP, increased PGE2 generation in the pancreas (by 45%), reversed the histological manifestations of pancreatitis, reduced the rise in amylase blood level and improved PBF. Administration of nonselective inhibitor of COX; indomethacin (5 or 10 mg/kg i.p.) prior to the injection of LPS abolished its protective effects on CIP and reduced pancreatic PGE2 generation. Selective inhibitor of COX-1; resveratrol (10 mg/kg i.p.) given prior to the injection of LPS reversed its protective effects against CIP. Pretreatment with a selective inhibitors of COX-2: rofecoxib or NS-398 (10 mg/kg) attenuated LPS-induced pancreatic protection in the CIP rats. COX-1 expression was detected in the intact pancreas and was not signif

Topics: Acute Disease; Amylases; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ceruletide; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Enzyme Inhibitors; Indomethacin; Isoenzymes; Lactones; Lipopolysaccharides; Male; Membrane Proteins; Nitric Oxide; Nitric Oxide Donors; Nitroarginine; Nitrobenzenes; Organ Size; Pancreas; Pancreatitis; Penicillamine; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Resveratrol; S-Nitroso-N-Acetylpenicillamine; Stilbenes; Sulfonamides; Sulfones

We have previously shown that long-term potentiation (LTP) decreases the sensitivity of glutamate receptors in the rat hippocampal CA1 region to exogenously applied glutamate agonists. Since the pathophysiology of hypoxia/ischemia involves increased concentration of endogenous glutamate, we tested the hypothesis that LTP could reduce the effects of hypoxia in the hippocampal slice. The effects of LTP on hypoxia were measured by the changes in population spike potentials (PS) or field excitatory post-synaptic potentials (fepsps). Hypoxia was induced by perfusing the slice with (i) artificial CSF which had been pre-gassed with 95%N2/5% CO2; (ii) artificial CSF which had not been pre-gassed with 95% O2/5% CO2; or (iii) an oxygen-glucose deprived (OGD) medium which was similar to (ii) and in which the glucose had been replaced with sucrose. Exposure of a slice to a hypoxic medium for 1.5-3.0 min led to a decrease in the PS or fepsps; the potentials recovered to control levels within 3-5 min. Repeat exposure, 45 min later, of the same slice to the same hypoxic medium for the same duration as the first exposure caused a reduction in the potentials again; there were no significant differences between the degree of reduction caused by the first or second exposure for all three types of hypoxic media (P>0.05; paired t-test). In some of the slices, two episodes of LTP were induced 25 and 35 min after the first hypoxic exposure; this caused inhibition of reduction in potentials caused by the second hypoxic insult which was given at 45 min after the first; the differences in reduction in potentials were highly significant for all the hypoxic media used (P<0.01; paired t-test). The neuroprotective effects of LTP were not prevented by cyclothiazide or inhibitors of NO synthetase compounds that have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to those of propentofylline, a known neuroprotective compound. We conclude that LTP causes an appreciable protection of hippocampal slices to various models of acute hypoxia. This phenomenon does not appear to involve desensitisation of AMPA receptors or mediation by NO, but may account for the recognised inverse relationship between educational attainment and the development of dementia.

Topics: Action Potentials; Acute Disease; Animals; Benzothiadiazines; Carbon Dioxide; Cell Hypoxia; Culture Media, Serum-Free; Electric Stimulation; Excitatory Postsynaptic Potentials; Glucose; Hippocampus; Hypoxia-Ischemia, Brain; Long-Term Potentiation; Male; Neuroprotective Agents; Nitroarginine; Oxygen; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Sucrose; Xanthines

Lipopolysaccharide (LPS) derived from the bacterial cell wall activates the inflammatory response in the tissue but the role of LPS in the pathogenesis of pancreatic damage and in the activation of NO system in the pancreas has not been fully explained. The aim of this study was to investigate the effect of repeated administration of LPS to the rats on the integrity of the pancreas, on the ability of isolated pancreatic acini to secrete the amylase and on the plasma level of tumor necrosis factor alpha (TNFalpha). The role of NO in the pancreatic resistance to the damage was assessed in animals subjected to repeated administration of LPS. To induce pancreatic damage one group of rats received intraperitoneal (i.p.) injection of LPS (from E. coli) every day during 5 consecutive days (10 mg/kg--day). Another groups of animals were given N(G)-nitro-L-arginine (L-NNA), an inhibitor of NO synthase (NOS) (20 mg/kg i.p.) alone or in combination with L-arginine (100 mg/kg i.p.), 30 min prior to each LPS injection. Plasma level of TNFalpha was determined by ELISA kit. Repeated administration of LPS produced mild pancreatic inflammation that was most pronounced at day 5 of LPS treatment and manifested as edema, neutrophil infiltration and hemorrhage of the pancreas. The survival rate after 5 days treatment with LPS was 87.5%. Pancreatic weight, plasma levels of TNFalpha and amylase, pancreatic blood flow (PBF) and NO generation by pancreatic acini were markedly increased in rats subjected to repeated administration of LPS whereas the amylase response of isolated pancreatic acini to pancreatic secretagogues was significantly attenuated. Suppression of NOS by L-NNA resulted in a dramatic increase in the mortality of the animals reaching 50% and significantly increased inflammatory changes in the pancreatic tissue, decreased PBF, abolished the ability of pancreatic acini to release NO and to secrete amylase. Pancreatic weight and plasma levels of amylase and TNFalpha significantly increased in the group of rats treated with combination of LPS+L-NNA as compared to the animals received LPS alone. Addition of L-arginine to L-NNA+LPS administration reversed all harmful effects produced by L-NNA in the pancreas. We conclude that repeated administration of high doses of bacterial LPS to the rats could induce pancreatic tissue damage by itself, however, it is not able to produce severe pancreatitis. Suppression of NO generation significantly aggravates the pancreatic lesion

Topics: Acute Disease; Amylases; Animals; Disease Models, Animal; Enzyme Inhibitors; Lipopolysaccharides; Male; Nitric Oxide; Nitroarginine; Organ Size; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regional Blood Flow; Survival Analysis; Tumor Necrosis Factor-alpha

The aim of this study was to examine the effects of nitric oxide synthase inhibition on antigen- and histamine-induced acute airway reactions, in order to clarify the possible modulating role of NO. Twelve specific-pathogen-free pigs (sensitized with Ascaris suum antigen) were challenged with an antigen aerosol during mechanical ventilation and anaesthesia. Six pigs were pretreated with N(G)-nitro-L-arginine (L-NA, 10 mg x kg(-1)), a NO synthase inhibitor, 30 min before challenge. In separate experiments, seven sensitized pigs received histamine (5 mg) aerosols before and after L-NA treatment. It was found that pretreatment with L-NA resulted in an enhanced airways resistance response to antigen (areas under the curve 0-90 min were (mean+/-SEM) 1,119+/-160 versus 555+/-56 (cmH2O x L(-1) x s(-1) x min for controls, p<0.05 (Mann-Whitney U-test), whereas this response to histamine was not affected by L-NA. Moreover, L-NA pretreatment significantly enhanced total protein (1.85+/-0.43 versus 0.31+/-0.06 g x L(-1), p<0.01) and histamine levels (42.8+/-16.0 versus 2.6+/-0.8 nM, p<0.05) in bronchoalveolar lavage fluid 45 min after antigen challenge. In conclusion, this study showed that N(G)-nitro-L-arginine enhanced reactions occurring during the acute allergic reaction in pigs in vivo. This indicates a protective role of nitric oxide, which might occur through downregulation of histamine release from mast cells rather than a direct bronchodilating effect of nitric oxide.

Topics: Acute Disease; Airway Resistance; Animals; Antigens, Helminth; Ascaris suum; Bronchi; Bronchoalveolar Lavage Fluid; Cardiovascular System; Enzyme Inhibitors; Gases; Histamine; Hydrogen-Ion Concentration; Hypersensitivity; Inflammation Mediators; Lung Compliance; Nitric Oxide Synthase; Nitroarginine; Swine

Little is known about the changes in hepatic blood flow associated with acute hepatic injury. The aim of this study was to investigate the effect of nitric oxide (NO) on hepatic blood flow and the severity of hepatic injury in rats with carbon tetrachloride (CCl4)-induced acute hepatic injury.. Rats were pretreated with CCl4 to induce acute hepatic injury. Hepatic blood flow was measured using a radioactive microsphere method. The role of NO in the regulation of hepatic blood flow and the severity of hepatic injury was investigated by administering NG-nitro-L-arginine (L-NNA) and aminoguanidine (AG). Plasma nitrite/nitrate levels, hepatic NO synthase (NOS) activity, and expression of hepatic NOS messenger RNA (mRNA) were measured, and histological examinations were performed.. Hepatic arterial and portal venous blood flow was increased significantly by CCl4, without any change in mean arterial pressure or cardiac output. L-NNA and AG dose-dependently decreased hepatic arterial blood flow, with the highest dose resulting in complete blockade of hepatic arterial dilation, but failed to change portal venous blood flow. Histologically, administration of AG aggravated the hepatic injury in CCl4-treated rats. Plasma nitrite/nitrate levels and hepatic NOS activity were increased significantly by CCl4 treatment. Inducible NOS mRNA was detected in CCl4-treated rats but not in the controls.. The results of this study suggest that the increased hepatic arterial blood flow in CCl4-induced acute hepatic injury is mediated by excessive NO production and up-regulated by inducible NOS, which plays a role in reducing hepatic injury.

Topics: Acute Disease; Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Enzyme Inhibitors; Guanidines; Hepatic Artery; Liver; Liver Circulation; Liver Diseases; Male; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitrites; Nitroarginine; Rats; Rats, Sprague-Dawley; Regional Blood Flow; RNA, Messenger

The aim of the study was to investigate the impact of L-arginine (nitric oxide donor), L-NNA (NO synthase inhibitor), heparin and procaine on the pancreas' microcirculation, serum interleukin 6 (IL-6) level, and microscopic alterations of the pancreatic gland in acute pancreatitis (AP) in rats. AP was induced by 4 i.p. injections of cerulein (15 micrograms/kg/h). Microcirculatory values of the pancreas were measured by means of laser Doppler flowmetry 5 h after the first cerulein injection. Remarkable morphologic changes in the pancreas, including parenchymal necrosis, an elevation of serum IL-6 activity, and significant drop of pancreatic capillary perfusion was observed in rats with NO synthase inhibition. L-arginine improved the pancreatic microcirculation but worsened the microscopic alterations within the pancreas. Heparin had a beneficial effect on the microcirculatory values, serum IL-6 activity, and morphologic changes. Procaine had no effect on the course of AP. Authors conclude that heparin, improving the pancreatic capillary blood perfusion, may be considered as a promising therapeutic agent in acute pancreatitis.

Topics: Acute Disease; Animals; Arginine; Ceruletide; Heparin; Interleukin-6; Male; Microcirculation; Nitric Oxide; Nitroarginine; Pancreas; Pancreatitis; Procaine; Rats; Rats, Wistar

Our aim was to investigate the possible involvement of nitric oxide (NO) in peripheral denervation during the acute phase of murine experimental Trypanosoma cruzi infection. Wistar male rats were infected with the Y strain of T. cruzi. One group of animals was also treated with the NO synthase inhibitor N-nitro-l-arginine. A group of uninfected animals was the control. At the 18th day of infection the animals were sacrificed. Quantification of neurons in the colon and heart and tissue parasitism in the heart was performed. Serum concentration of nitrate was measured and a histochemical technique for assessing NADPH-diaphorase activity in the colon was also performed. The infected animals presented a statistically significant decrease in the number of peripheral neurons in the colon and heart and a 2-fold increase in serum NO(3) concentration compared with controls. The animals treated with N-nitro-l-arginine showed almost an absence of NO(3) concentration in the serum and did not show loss of neurons compared with controls. These treated animals displayed a 15-fold increase in tissue parasitism compared with nontreated infected animals. The NADPH-diaphorase activity was much more intense in the muscle layers of the colon of the infected animals than in those of the controls. Taken together, these data suggest that NO is involved in the peripheral denervation observed in the acute phase of experimental T. cruzi infection.

Topics: Acute Disease; Animals; Autonomic Nervous System; Chagas Disease; Colon; Enzyme Inhibitors; Heart Atria; Male; Muscle, Smooth; Myenteric Plexus; Myocardium; NADPH Dehydrogenase; Neurons; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Wistar

Nitric oxide (NO) as a unique biological mediator that has been implicated in many physiological and pathophysiological processes may have a significant influence on the course of acute pancreatitis and the recovery process. The aim of the study was to evaluate the effect of a NO synthase inhibitor or a substrate for NO endogenous production on the ultrastructural features of the acinar cells in the course of caerulein-induced acute pancreatitis. Acute pancreatitis was induced in the rats by a supramaximal dose of caerulein. During acute pancreatitis induction, the rats were treated with L-arginine (the substrate for NO synthesis), NG-nitro-L-arginine (L-NNA, NO synthase inhibitor), L-arginine + L-NNA or saline. Light and electron microscopy examinations were performed in all groups after pancreatitis induction and additionally after 7 and 14 days of recovery. The study demonstrated that the NO synthase inhibitor given during pancreatitis induction in rats enhances the damage to the acinar cells, detected ultrastructurally, and increases the cellular inflammatory infiltration. In the later period, the considerable damage to the mitochondria and the changes in secretory compartment were observed, including dilated cisternae of Golgi apparatus, focal degranulation of rough endoplasmic reticulum, and reduced number of zymogen granules and condensing vacuoles. L-arginine reversed to some extent the deleterious effect of L-NNA, although when administered alone it had no apparent effect on the ultrastructure of pancreatic acinar cells compared with untreated animals. The obtained results indicate that the NO synthase inhibitor enhances the ultrastructural degenerative alterations in the pancreatic acinar cells in the course of caerulein-induced acute pancreatitis and confirm the protective role of endogenous nitric oxide in this disease.

Topics: Acute Disease; Animals; Arginine; Ceruletide; Enzyme Inhibitors; Male; Microscopy, Electron; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Pancreas; Pancreatitis; Rats; Rats, Wistar

Nitric Oxide's (NO) function in vasomotor control, inflammation, and signal transduction makes it an attractive potential mediator of the capillary leak seen in acute lung injury. Despite extensive study, the role of NO in intestinal ischemia/reperfusion-induced capillary leak remains controversial. Rats were treated with vehicle, norepinephrine, or L-NNA (nitric oxide synthase inhibitor) and then underwent sham laparotomy or 30 min SMA occlusion followed by 1 to 12 h of reperfusion. Evan's Blue dye was administered 1 h before animals were euthanized. Ratios of bronchoalveolar lavage or small-intestine lavage to serum dye concentrations were calculated as measures of capillary leak. Circulating neutrophil activation was measured with a nitroblue tetrazolium reduction assay. In vehicle-treated animals, both capillary leakage and PMN activation peaked at 4 h of reperfusion. These parameters returned to baseline by 12 h. Treatment with L-NNA accelerated ischemia/reperfusion-induced PMN activation as well as accelerated capillary leak from 4 to 1 h. Treatment with norepinephrine (hypertensive control) increased the magnitude of lung capillary leak but had no effect on the timing of ischemia/reperfusion-induced PMN activation or ischemia/reperfusion-induced capillary leak. These data show that intestinal ischemia/reperfusion-induced systemic capillary leak is associated with systemic neutrophil activation. Nitric oxide synthase inhibition accelerates ischemia/reperfusion-induced capillary leak and mediates the capillary leak seen in acute lung injury by modulating neutrophil activation.

Topics: Acute Disease; Animals; Bronchoalveolar Lavage Fluid; Capillaries; Enzyme Inhibitors; Male; Neutrophil Activation; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Norepinephrine; Pulmonary Circulation; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Respiratory Distress Syndrome; Vasoconstrictor Agents

Cholestasis liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, increased plasma total activity, and elevated plasma enkephalin concentrations. The effect of the nitric oxide (NO) synthase inhibitor, L-nitro-arginine (L-NA, 0.03, 0.1, 0.3, 1 mg/kg), and the nitric oxide precursor, L-Arg (30 mg/kg), on antinociception induced by bile duct resection or sham operation, as well as on opioid dependence, was examined in male albino Swiss mice. Repeated (5 days) administration of L-NA attenuated signs of dependence, as assessed by naloxone (5 mg/kg)-precipitated withdrawal, and decreased the antinociception; however, L-Arg potentiated withdrawal signs and increased the antinociception. The results of this study support the involvement of the L-arginine/nitric oxide pathway in the opioidergic-dependent manifestation of cholestasis in an animal model.

Topics: Acute Disease; Animals; Arginine; Behavior, Animal; Bile Ducts; Cholestasis; Enzyme Inhibitors; Male; Mice; Naloxone; Narcotic Antagonists; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Reaction Time; Substance Withdrawal Syndrome

Topics: Acute Disease; Animals; Arachidonic Acid; Arginine; Endotoxemia; Enzyme Inhibitors; Humans; Infant, Newborn; Lipopolysaccharides; Male; Nitric Oxide Synthase; Nitroarginine; Rabbits; Rats; Rats, Sprague-Dawley; Respiratory Distress Syndrome, Newborn

The behavior of neutrophils in a rat acute pancreatitis model was observed in the pancreas and liver using fluorescence microscopy with an image analyzing system after labeling with a specific fluorescent reagent. Nonviable cells of both organs were also labeled and quantified. The role of nitric oxide in neutrophil accumulation and organ damage was estimated by administering a relatively selective inhibitor of constitutive nitric oxide synthase, N-nitro-L-arginine (L-NNA). The animal model of acute pancreatitis was induced by cerulein injection (80 mg/kg). Two groups were created, one given and the other not given L-NNA (2.5 mg/kg) prior to the induction of pancreatitis. The number of accumulated neutrophils in the pancreas and liver increased in a time-dependent manner. There was a close relation between the distribution of the neutrophils and inviable acinar cells or hepatocytes. When pretreated with L-NNA, the numbers of accumulated neutrophils and nonviable cells increased significantly in the pancreas. In the liver, a more pronounced accumulation of neutrophils was observed after treatment with L-NNA. Although hepatocyte injury was mild despite the neutrophil accumulation in the control, such injury was marked in the group treated with L-NNA. This suggests that neutrophils serve an important role in exacerbating acute pancreatitis and that nitric oxide provides a defense mechanism against neutrophil accumulation in pancreas and liver.

Topics: Acute Disease; Animals; Capillaries; Cell Adhesion; Ceruletide; Enzyme Inhibitors; Liver; Male; Neutrophils; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Pancreas; Pancreatitis; Rats; Rats, Wistar; Venules

Local microcirculatory dysfunction within the pancreatic gland might be an important factor in the conversion of oedematous to necrotizing pancreatitis. Therapeutic agents, improving the pancreatic blood flow, might be valuable in acute pancreatitis treatment. An influence of nitric oxide, heparin and procaine treatment on microcirculatory values in acute pancreatitis (AP) in rats was investigated. Acute pancreatitis was induced by i.p. injection of cerulein in four doses of 15 microg kg-1 each at 1-h intervals. The rats with pancreatitis were divided into five groups, 12 animals each. One group remained without treatment, four groups were treated i.p. either with NO synthase inhibitor L-NNA (2x25 mg kg-1 or heparin 2x2.5 mg kg-1 or L-arginine 2x100 mg kg-1 or procaine 2x25 mg kg-1. Five control groups, ten animals each, received saline, L-NNA, heparin, L-arginine or procaine only. Five hours after the first ceruleine injection microcirculatory values within the pancreas were measured by means of laser Doppler flowmetry. Acute pancreatitis caused a significant drop of microcirculatory value to 37% of the basal value. The L-NNA administration resulted in a further insignificant reduction of the pancreatic blood flow to 34%. An improvement of microcirculation was observed in rats with pancreatitis receiving heparin (76%) and L-arginine (72%). Procaine had no effect on microcirculatory disturbances within the pancreas in rats with pancreatitis. Cn-induced acute pancreatitis (AP) causes microcirculatory deterioration within the pancreas. Heparin and nitric oxide donor, L-arginine, might be considered as therapeutic agents, improving the diminished pancreatic tissue perfusion observed in acute pancreatitis. Procaine does not improve the pancreatic blood flow in acute pancreatitis.

Topics: Acute Disease; Animals; Arginine; Ceruletide; Heparin; Male; Microcirculation; Nitroarginine; Pancreas; Pancreatitis; Procaine; Rats; Rats, Wistar

Tissue nitric oxide (NO) concentration was investigated in relation to ion-homeostasis disturbance in the cat model of focal cerebral ischaemia. An NO electrode, a Ca2+ microelectrode and a laser Doppler probe were applied to the cerebral cortex in the core and periphery of the middle cerebral artery. NO concentration increased by 25.1 +/- 6.3 nM at 5 min in severely ischaemic regions exhibiting anoxic depolarization (n = 5, p < 0.0005). This occurred with no reduction in extracellular Ca2+ concentration and before a massive Ca2+ influx into cells started several minutes later. The NO increase was abolished by NG-nitro-L-arginine treatment (n = 6, p < 0.05) and was absent in regions with no depolarization (n = 5, p < 0.0005). We conclude that the early increase in NO associated with depolarization is achieved by activation of constitutive NO synthase, possibly triggered by intracellular Ca2+ release.

Topics: Acute Disease; Animals; Biosensing Techniques; Blood Pressure; Body Temperature; Brain Ischemia; Calcium; Cats; Cerebrovascular Circulation; Electrophysiology; Enzyme Inhibitors; Extracellular Space; Female; Hypoxia, Brain; Laser-Doppler Flowmetry; Microelectrodes; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine

Nitric oxide (NO) has been implicated to regulate pancreatic circulation, promote capillary integrity, and inhibit leukocyte adhesion. We investigated the role of NO in the development of pancreatitis. Nitro-L-arginine, an inhibitor of NO synthase, in total dose of 35 mg/kg body wt was infused in the rats with edematous pancreatitis induced by two intraperitoneal injections of cerulein (20 micrograms/kg). L-Arginine (125 or 250 mg/kg), a NO donor was intravenously administered twice in the rats with hemorrhagic pancreatitis induced by water-immersion stress plus two intraperitoneal injections of cerulein (40 micrograms/kg). The degree of pancreas edema, serum amylase levels, and histologic alterations were investigated. Nitro-L-arginine exacerbated cerulein-induced pancreatitis and caused a decrease in pancreatic blood flow. L-Arginine ameliorated the severity of hemorrhagic pancreatitis dose dependently and improved the pancreatic blood flow. These findings suggest that NO could confer protection against the development of hemorrhagic pancreatitis, probably through improvement of the pancreatic microcirculation.

Topics: Acute Disease; Animals; Arginine; Ceruletide; Drug Interactions; Edema; Enzyme Inhibitors; Gastrointestinal Hemorrhage; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Pancreas; Pancreatitis; Random Allocation; Rats; Rats, Sprague-Dawley; Time Factors

This study was designed to investigate the role of nitric oxide (NO) in the formation of pancreatic edema in caerulein-induced pancreatitis in rats. Pancreatitis was produced by two intraperitoneal injections of caerulein, and plasma amylase concentration, pancreatic edema index (pancreatic wet weight/body weight), and Evans blue extravasation (as a measure of vascular permeability) were evaluated 5 h after the first injection. Four doses (1, 2.5, 5, and 10 mg/kg) of NG-nitro-L-arginine (L-NNA), an NO synthase inhibitor, were subcutaneously administered at -0.5, 0.5, 1.5, 2.5, and 3.5 h after the first injection of caerulein. L-NNA significantly lowered the edema index, the wet/dry weight ratio of the pancreas, and Evans blue extravasation in the rats with pancreatitis. The maximal effect was obtained by L-NNA at a dose of 2.5 mg/kg; this inhibited the increase in pancreatic edema formation from the control value by 60%-70%. Intraperitoneal injections (20 mg/kg, five times) of L-arginine, a substrate for NO production, partly reversed the L-NNA-induced inhibition of pancreatic edema formation, but D-arginine, an enantiomer of L-arginine, did not show any effect. Plasma amylase concentrations were not significantly affected by any dose of L-NNA, nor were they affected by L- or D-arginine. These findings strongly suggest that endogenous NO plays an important role in the formation of pancreatic edema in caerulein-induced pancreatitis in rats, probably by increasing vascular permeability and protein extravasation.

Topics: Acute Disease; Amylases; Animals; Arginine; Capillary Permeability; Ceruletide; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Evans Blue; Male; Nitric Oxide; Nitroarginine; Pancreatitis; Rats; Rats, Wistar

The role of NO during the first hour of endotoxemia is still controversial. To evaluate whether NO is protective or detrimental to the regulation of systemic blood pressure, cardiac output (CO), and organ perfusion in rats during acute endotoxemia, we have studied the effects of inhibition of NO synthesis. Thirty minutes after 0.1 mg NG-nitro-L-arginine (L-NNA; group L, n = 7, partial inhibition), 1 mg L-NNA (group H, n = 6, complete inhibition), or saline (group E, n = 7) intravenous infusion, anesthetized volume-loaded rats were infused with endotoxin Escherichia coli O127:B8 (8 mg.kg-1 x h-1) from time (t) = 0 to 60 min. Organ blood flow was measured with radioactive microspheres. In group H, at time 0, CO was lower than in group E (by -29%; P < 0.05), and systemic vascular resistance (SVR) was higher than in groups E and L (by 72 and 51%, respectively; P < 0.05). Perfusion of the pancreas, stomach, intestines, and kidney was lower (P < 0.05) and corresponding organ vascular resistance (OVR) higher (P < 0.05) in group H than in groups E and L (except kidney in group L). At t = 60 min, in groups H and L, CO was lower (by -45 and -26%, respectively; P < 0.05) and SVR was higher (by 112 and 54%, respectively; P < 0.05) than in group E. In group L only blood flow to the heart, pancreas, intestines, and kidney was significantly lower than in group E, and corresponding OVR was higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Arginine; Blood Pressure; Cardiac Output; Endotoxins; Hemodynamics; Male; Nitrates; Nitric Oxide; Nitrites; Nitroarginine; Rats; Rats, Wistar; Regional Blood Flow; Vascular Resistance

Topics: Acute Disease; Animals; Arginine; Cerebrovascular Circulation; Disease Models, Animal; Endothelium, Vascular; Hemodynamics; Homeostasis; Hypoxia; Infusions, Intravenous; Nitric Oxide; Nitroarginine; Oxygen Consumption; Pulmonary Circulation; Streptococcal Infections; Streptococcus agalactiae; Swine