nitroarginine and Pancreatitis

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

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

The goal of our study was to evaluate the influence of NO synthesis modulation on the ultrastructural changes in the pancreatic acinar cells in connection with morphometric assessment of the volume and numerical densities of mitochondria (Vvm, Nvm) and zymogen granules (Vvz, Nvz) in caerulein-induced acute pancreatitis (AP). During AP induction rats were treated with L-arginine--substrate for NO synthesis, N(G)-nitro-L-arginine (L-NNA)--NO synthase inhibitor, gliceryl trinitrate (NTG)--NO donor, L-arginine+L-NNA or saline. This study demonstrated that administration of L-NNA leads to the formation of numerous, large autophagosomes and mitochondria oedema in pancreatic acinar cells. Treatment with L-arginine or NTG during AP induction resulted in a diminution of the ultrastructural changes with a concomitant increase of Vvz. Vvm and Nvm were significantly lower in the L-arginine treated group compared to the untreated AP. The results indicate that: L-NNA enhances damage to acinar cells which may be indicative of a protective role for endogenous NO in oedematous AP. The application of L-arginine or NTG decreases the damage to acinar cells evaluated ultrastructurally, suggesting the morphological changes accompanying the onset of AP in rats after the administration of either substrate for endogenous NO synthesis or exogenous NO donor follow a favourable course.

Topics: Animals; Arginine; Ceruletide; Enzyme Inhibitors; Enzyme Precursors; Male; Microscopy, Electron; Mitochondria; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Nitroglycerin; Pancreas; Pancreatitis; Rats; Rats, Wistar; Secretory Vesicles

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

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 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

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

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

Microcirculatory disturbance may play an important role in the development of severe pancreatitis, leading the edematous form of the disease to the necrosis. The aim of this study was to investigate the impact of L-arginine (nitric oxide donor), L-NN (NO synthase inhibitor), and heparin on the pancreas microcirculation, serum interleukin-6 level and microscopic alterations of the pancreas in acute pancreatitis in rats.. Acute pancreatitis was induced in 72 rats by four intraperitoneal injections of cerulein (CN) (15 micrograms/kg body weight). Microcirculatory values was measured by means of laser Doppler flowmetry five hours after the first cerulein injection. The animals were divided into the following groups (12 rats each), according to the kind of treatment: Group 1 (CN), Group 2 (CN + L-NNA), Group 3 (CN + L-arginine), Group 4 (CN + Heparin), Group 5 (Control), Group 6 (L-NNA), Group 7 (L-arginine), Group 8 (Heparin).. Remarkable morphologic changes in the pancreas including parenchymal necrosis, an elevation of serum IL-6 level, and significant drop of pancreatic capillary perfusion was observed in rats with NO synthase inhibition. L-arginine improved the pancreatic microcirculatory but worsened the microscopic alteration within the pancreas. Heparin had a beneficial effect on the microcirculatory values, serum IL-6 concentration, and morphologic changes.. Acute pancreatitis causes microcirculatory disturbance within the pancreatic gland. The inhibition of NO synthase aggravates AP. L-arginine treatment improves pancreatic perfusion but potentiates morphologic alterations. Heparin has beneficial impact on AP, it improves the microcirculation and inflammatory changes within the pancreatic gland.

Topics: Analysis of Variance; Animals; Arginine; Ceruletide; Heparin; Interleukin-6; Microcirculation; Nitric Oxide; Nitroarginine; Pancreas; Pancreatitis; Rats

Stimulation of afferent neurons by capsaicin exerts protective activity against cerulein-induced pancreatitis. This action is dependent on endogenous release of nitric oxide (NO). Deactivation of afferent neurons by high doses of capsaicin contributes to the severity of pancreatitis. This action involves mainly decreased pancreatic blood flow (PBF). Afferent nerves and NO cooperate in the maintenance of the integrity of pancreatic tissue.. Stimulation of capsaicin-sensitive afferent fibers protects gastric mucosa against damage and causes changes in mucosal blood flow. The aim of the present study was to determine the role of stimulation or ablation of capsaicin-sensitive neurons and NO in the course of cerulein-induced pancreatitis in the rat.. Low and high doses of capsaicin were administered to animals with pancreatitis and to those without pancreatitis. The effect of several parameters was assessed. NO activity was blocked by NG-nitro-L-arginine.. We found that a low dose of capsaicin administered intragastrically caused an increase in PBF. A neurotoxic dose of capsaicin caused a decrease in PBF, RNA content, and DNA synthesis. Pancreatitis led to a significant decrease in PBF and DNA synthesis, but an increase in pancreatic weight, protein content, plasma amylase concentration, and neutrophil adherence. Stimulatory doses of capsaicin attenuated the pancreatic tissue damage of pancreatitis, and alteration of PBF, DNA synthesis, and neutrophil adherence. Capsaicin-induced ablation of afferent neurons caused an increase in all indicators of pancreatic damage. Blocking NO enhanced pancreatic damage, and this was reversed by addition of L-arginine.

Topics: Animals; Arginine; Capsaicin; Ceruletide; Dose-Response Relationship, Drug; Enzyme Inhibitors; Male; Neurons, Afferent; Nitric Oxide; Nitroarginine; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regional Blood Flow

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 aim of the present study was to determine the role of endogenous nitric oxide (NO) in pancreatic secretion in vivo and amylase release from pancreatic acini in vitro and in caerulein-induced acute pancreatitis in rats. Blockade of NO synthase by NG-nitro-L-arginine (L-NNA) (2.5 mg/kg i.v.) significantly reduced basal pancreatic protein secretion and that induced by the infusion of CCK (0.5 micrograms/kg-h), feeding, and the diversion of pancreatic juice in rats with pancreatic fistula. This inhibitory effect was partially reversed when L-arginine (50 mg/kg-h i.v.) was added to L-NNA. L-Arginine alone (50 mg/kg i.v.) did not affect basal or caerulein-induced pancreatic secretion. L-NNA, L-arginine, or their combination added in various concentrations to the incubation medium of dispersed acini failed to affect basal or secretagogue (caerulein or urecholine) stimulated amylase release. Infusion of caerulein (5 micrograms/kg-h) for 5 h produced histological changes of acute edematous pancreatitis accompanied by a marked increase in pancreatic protein content and about 50% reduction in tissue blood flow. L-NNA alone also reduced the pancreatic blood flow and caused a significant increase in pancreatic weight and protein content. L-NNA significantly potentiated the inflammatory changes in the pancreas caused by caerulein. Addition of L-arginine enhanced the pancreatic blood flow and ameliorated the pancreatitis induced by caerulein alone or that combined with L-NNA. We conclude that NO is involved in the stimulation of pancreatic secretion in vivo and exhibits a beneficial effect on pancreatitis, probably by improving the pancreatic blood flow.

Topics: Amylases; Animals; Arginine; Ceruletide; In Vitro Techniques; Male; Nitric Oxide; Nitroarginine; Pancreas; Pancreatitis; Rats; Rats, Wistar; Sincalide