L-Arginine, nitric oxide, and intestinal secretion: studies in rat jejunum in vivo (original) (raw)
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Effects of L-Arginine and L-NAME on Duodenal Histologic Parameters in Female Wistar Rats
Introduction: Nitric oxide (NO), as a free radical, involves in several physiologic functions in GI tract such as nerve impulse transmission and vascular tonicity regulation. Nitric oxide synthase (NOS) is the enzyme for the production of NO from L-Arginine which in turn inhibits by L-NGNitroarginine Methyl Ester (L-NAME). In the current work, we aimed to evaluate morphometric analysis of duodenum under exposure of L-Arginine and L-NAME in female Wistar rats. Methods: In this study, 5 groups (N=8) of 40 female rats (200-250 g, 8 weeks age) were chosen. Normal saline (2 mL/kg), L-Arginine (200 mg/kg), L-NAME (20 mg/kg) and L-Arginine+LNAME (with the same doses) were administered intraperitoneal — for 3 days. After 2 weeks, samples were collected, stained with hematoxylin and eosin (H&E) and observed under light microscopy. Duodenal epithelial cell height and number, gland diameter, and submucosal and muscular thicknesses were measured using optical software and analyzed by one-way ANOVA followed by Tukey’s post hoc test using SPSS-16. P≤ 0.05 was considered statistically significant. Results: There were no significant changes in mean variables compared to the control group. Conclusion: The results attested no noticeable changes in regard with the effects of L-arginine and L-NAME on duodenum parameters despite the major roles of NO in GI tract.
The Journal of Physiology, 2003
Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) interact in the regulation of neuromuscular function in the gut. They are also potent intestinal secretogogues that coexist in the enteric nervous system. The aims of this study were: (1) to investigate the interaction between NO and VIP in inducing fluid secretion in the rat jejunum, and (2) to determine whether the NO effect on intestinal fluid movement is neurally mediated. The single pass perfusion technique was used to study fluid movement in a 25 cm segment of rat jejunum in vivo. A solution containing 20 mM L-arginine, a NO precursor, was perfused into the segment. The effect of the NO synthase inhibitors (L-NAME and L-nitroindazole (L-NI)) and the VIP antagonist ([4Cl-D-Phe 6 ,Leu 17 ]VIP (VIPa)) on L-arginine-induced changes in fluid movement, expressed as ml min _1 (g dry intestinal weight) _1 , was determined. In addition, the effect of neuronal blockade by tetrodotoxin (TTX) and ablation of the myenteric plexus by benzalkonium chloride (BAC) was studied. In parallel groups of rats, the effect of L-NAME and L-NI on VIP-induced intestinal fluid secretion was also examined. Basal fluid absorption in control rats was (median (interquartile range)) 65 (45-78). L-Arginine induced a significant fluid secretion (_14 (_20 to _5); P < 0.01). This effect was reversed completely by L-NAME (60 (36-65); P < 0.01) and L-NI (46 (39-75); P < 0.01) and partially by VIPa (37 (14-47); P < 0.01). TTX and BAC partially inhibited the effect of L-arginine (22 (15-32) and 15 (10-26), respectively; P < 0.05). The effect of VIP on fluid movement (_23 (_26 to _14)) was partially reversed by L-NAME (24 (8.4-35.5); P < 0.01) and L-NI (29 (4-44); P < 0.01). The inhibition of VIP or NO synthase prevented L-arginine-and VIP-induced intestinal fluid secretion through a neural mechanism. The data suggest that NO enhances the release of VIP from nerve terminals and vice versa. Subsequently, each potentiates the other's effect in inducing intestinal fluid secretion.
Role ofl-arginine, a substrate for nitric oxide-synthase, in gastroprotection and ulcer healing
Journal of Gastroenterology, 1997
Nitric oxide (NO) synthesized from L-arginine interacts with prostaglandins (PG) and sensory neuropeptides in the regulation of mucosal integrity, but the role of L-arginine, a substrate for NO-synthase, in gastroprotection and healing of chronic gastric ulcers has been little studied. In this study we compared the effects of intragastric (i.g.) and systemic (i.v.) administration of L-arginine or D-arginine on gastric secretion and acute gastric lesions provoked in rats by i.g. application of 100% ethanol, acidified aspirin (ASA), or the exposure to 3.5 h of water immersion and restraint stress (WRS). In addition, the effects of L-arginine on ulcer healing and the formation of new vessels (angiogenesis) were determined, using monoclonal antibody (MAb E-9). L-arginine (10-200mg/kg i.g.) failed to significantly affect gastric secretion but dose-dependently reduced the gastric lesions induced by 100% ethanol, ASA, and WRS, the doses inhibiting 50% of these lesions being 65, 94, and 72mg/kg, respectively. This protection was accompanied by a significant rise in the gastric blood flow (GBF), whereas L-arginine given i.v. failed to affect the ethanol-lesions and the GBF. D-arginine or the NOrelated amino acids-L-glutamine, L-citrulline, or Lornithine-failed to significantly influence these lesions. Suppression of the generation of mucosal PG by indomethacin or capsaicin-denervation attenuated the protection and hyperemia induced by L-arginine. The inhibition of constitutive NO synthase by L-NNA had no significant effect on the protection afforded by Larginine, but reduced the gastric hyperemia accompanying this protection. L-arginine (150mg/kg per day, i.g.
Protective Effects of L-Arginine on Rat Terminal Ileum Subjected to Ischemia/Reperfusion
Journal of Pediatric Gastroenterology and Nutrition, 2008
Objectives: Studies have shown that nitric oxide (NO) may play a major role in sustaining mucosal integrity; however, NO has been also implicated in the pathogenesis of ischemia/ reperfusion (I/R)-related tissue injury. We investigated the effects of L-arginine and N G-nitro L-arginine methyl ester (L-NAME) on the acetylcholine-induced contractile response of ileum and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). Histopathological changes were also evaluated in ileal preparations. Materials and Methods: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (3 hours). Four groups were designed: shamoperated control; I/R; I/R and L-arginine pretreatment; and I/ R and L-NAME pretreatment. After reperfusion, ileum specimens were collected to determine the parameters mentioned above. Results: Following reperfusion, a significant decrease in acetylcholine-induced contractile response, an increase in lipid peroxidation, a decrease in GSH content, and mucosal damage of the ileal preparations were observed. We showed that decreased contractility, increased lipid peroxidation, and reduced GSH content have been reversed by L-arginine but not by L-NAME. Mucosal injury was significantly lowered in the L-arginine group. Conclusions: Treatment with L-arginine exerted a protective effect in intestinal I/R injury, which was mediated in part by regulating MDA and GSH levels, consequently ameliorating impaired contractile response and mucosal injury. JPGN 46:29-35, 2008.
Transplantation Proceedings, 2008
Objective. Usualy an experimental necrotizing enterocolitis experimental model, we Investigated nitric oxide levels in intestinal tissues of newborn mice with or without L-arginine therapy during sessions of ischemia and reoxygenation. Methods. Twenty-six newborn mice from the Wistar EPM-1 lineage, weighing from 4.5 to 6.2 g, were randomly assigned to three groups: G-I/R, hypoxia and reoxygenation; G-Arg, L-arginine treatment I/R; and G-CTL, controls. G-I/R and G-Arg mice underwent twice a day during their first 3 days of life exposure to gas chambers with 100% CO 2 for 5 minutes at 22°C before reoxygenation with 100% O 2 for another 5 minutes. After 12 hours, all animals were sedated, laparotomized, and had samples of ileum and colon taken and-either formalin fixed histopathologic examations or frozen to Ϫ80°C for estimation of tissue nitric oxide levels. Intestinal injuries were classified according to the criteria of Chiu et al. Results. The G-I/R and G-Arg groups showed injuries characteristic of necrotizing enterocolitis (NEC) with an improved structural preservation rate in G-Arg. The concentration of nitric oxide in the Ileum was much higher with G-Arg (16.5 Ϯ 4.9; P ϭ 0.0019) G-I/R (7.3 Ϯ 2.0). This effect was not observed in the colon: G-I/R ϭ 10.7 Ϯ 4.6 versus G-Arg ϭ 15.5 Ϯ 8.7 (P ϭ .2480). Conclusion. Supply of L-arginine increased tissue levels of nitricoxide and reduced morphologic intestinal injury among mice undergoing I/R.
The American journal of physiology
Effects of long-term oral L-arginine on esophageal motility and gallbladder dynamics in healthy humans. Am. J. Physiol. 274 (Gastrointest. Liver Physiol. 37): G984-G991, 1998.-Inhibitory nitrergic neurons are known to play a role in the regulation of motility patterns of the distal esophagus, the lower esophageal sphincter (LES), and the gallbladder. Our study aim was to investigate the effects of ''long-term'' (i.e., prolonged) oral intake of L-arginine (L-Arg), the endogenous source for nitric oxide (NO) synthesis, on postprandial LES pressure (LESP), esophageal motility, gastroesophageal reflux, and gallbladder motility. L-Arg (30 g/day) or glycine (placebo; 13 g/day; isosmolar) was given orally to 10 healthy male volunteers for 8 days, according to a randomized, crossover design. Twenty-four-hour urinary nitrite/nitrate excretion was measured to indicate NO synthesis. Basal early postprandial LESP was lower after L-Arg ingestion (2.2 kPa) than after glycine ingestion (2.7 kPa) (P Ͻ 0.05). L-Arg abolished the physiological late postprandial rise in LESP. Transient LES relaxations were longer lasting after L-Arg ingestion (P Ͻ 0.02). Esophageal motility and reflux were not affected (not significant). Fasting and residual gallbladder volumes were greater after L-Arg ingestion (P Ͻ 0.05). Urinary nitrite/nitrate excretion was higher after L-Arg intake (P Ͻ 0.05). In conclusion, long-term oral L-Arg suppresses late postprandial LESP increase, prolongs transient LES relaxations, and increases fasting and residual gallbladder volumes. These effects may be mediated by increased NO synthesis.
European Journal of Nutrition, 2013
Background and aims Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) are important intestinal neurotransmitters that coexist in the gut enteric nervous system and play an important role in intestinal physiology (e.g., absorption, motility, fluid secretion and smooth muscle relaxation). It is also known that cold exposure alters several aspects of gastrointestinal physiology and induces hyperphagia to meet increased metabolic demands, but there are no data regarding NO and VIP involvement in intestinal response during acclimation to cold. The objective of this study was to determine the influence of longterm L-arginine supplementation on the expression of the three isoforms of nitric oxide synthase (NOS) and VIP in small intestine of rats acclimated to room temperature or cold. Methods Animals (six per group) acclimated to room temperature (22 ± 1°C) and cold (4 ± 1°C), respectively, were treated with 2.25 % L-arginine, a substrate for NOSs, or with 0.01 % N x-nitro-L-arginine methyl ester, an inhibitor of NOSs, for 45 days. The topographical distribution of VIP and NOSs expression in small intestine was studied by immunohistochemistry, and ImageJ software was used for semiquantitative densitometric analysis of their immunoexpression. Results Long-term dietary L-arginine supplementation increases VIP and NOSs immunoexpression at room temperature while at cold increases the endothelial NOS, inducible NOS and VIP but decrease neuronal NOS in rat small intestine. Conclusion Our results demonstrate that long-term dietary L-arginine supplementation modulates NOSs and VIP immunoexpression in rat small intestine with respect to ambient temperature, pointing out the eNOS as a predominant NOS isoform with an immunoexpression pattern similar to VIP.