Inhibitors of nitric oxide synthase enhance rat ileum contractions induced by ricinoleic acid in vitro (original) (raw)
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L-Arginine, nitric oxide, and intestinal secretion: studies in rat jejunum in vivo
Gut, 1996
Background-L-Arginine has been shown to induce fluid secretion in human jejunum. Nitric oxide, a derivative of L-arginne is thought to have an important role as an intestinal secretagogue. Aim-To determine the effect of Larginine and the nitric oxide synthase inhibitor, nitro L-arginine methyl ester (L-NAME), on fluid and electrolyte movement in rat jejunum. Methods-A 25 cm segment ofrat jejunum was perfused in situ with iso-osmotic solutions containing either (1) saline, (2) D-arginine 20, (3) L-arginine 20, (4) L-NAME 0-1, 1, or 20 mmol/l, or (5) a combination of L-arginine 20 and L-NAME 0.1, 1, or 20 mmol/l. In further groups the effect of a subcutaneous injection of L-NAME 100 mglkg was examined in rats pretreated with either Dor L-arginine 500 mg/kg. Results-L-Arginine, unlike D-arginine, induced fluid secretion despite being better absorbed (mean-7 3 v 17-0 ,l/min/ g; p<001). L-NAME at 0.1 mmol/l had no effect on basal fluid movement but reversed L-arginine induced secretion (7.8; p<005). L-NAME at 1 and 20 mmol/l induced fluid secretion (-15.4 and-28-4, respectively), which was enhanced by the addition of L-argilnlne (-30.0 and-41-0, respectively; both p<005). A subcutaneous injection of L-NAME resulted in marked fluid secretion (-39.9) and histological evidence of intestinal ischaemia. These changes were attenuated or reversed by pretreatment with subcutaneous L-but not D-arginine. Conclusions-L-Arginine induces intestinal fluid secretion through production of nitric oxide. There is a delicate balance between the effect of nitric oxide as a secretagogue and its effect on maintaining blood flow and thus preventing intestinal ischaemia.
Lack of anticholinergic effect of NG-nitro-l-arginine methylester in the small intestine
European Journal of Pharmacology, 1999
Ž . G Ž . The nitric oxide NO -synthase inhibitor, N -nitro-L-arginine methylester L-NAME , has been reported to have an atropine-like Ž . action. We compared the effects of L-NAME 1 mM and atropine on isolated small intestinal preparations of the guinea-pig, rat, rabbit Ž . and mouse. Half-maximal longitudinal contractions in response to acetylcholine 50-100 nM were not influenced by L-NAME, but were Ž . strongly suppressed by atropine 1 nM . Cholinergic 'twitch' contractions of the guinea-pig ileum were slightly enhanced by L-NAME; G Ž . this effect was prevented by pretreatment with N -nitro-L-arginine L-NOARG, 100 mM , another NO synthase inhibitor. 'Twitch' Ž . contractions were concentration dependently inhibited by atropine 1-100 nM . We conclude that L-NAME is free of atropine-like activity in isolated intestinal preparations. q
Mechanisms underlying the nitric oxide inhibitory effects in mouse ileal longitudinal muscle
Canadian Journal of Physiology and Pharmacology, 2005
We investigated the mechanisms involved in the nitric oxide (NO)-induced inhibitory effects on longitudinal smooth muscle of mouse ileum, using organ bath technique. Exogenously applied NO, delivered as sodium nitroprusside (SNP; 0.1–100 µmol/L) induced a concentration-dependent reduction of the ileal spontaneous contractions. 1H-[1,2,4]oxadiazolol[4,3,a]quinoxalin-1-one (ODQ; 1 µmol/L), a guanilyl cyclase inhibitor, reduced the SNP-induced effects. Tetraethylammonium chloride (20 mmol/L), a non-selective K+ channel blocker, and charybdotoxin (0.1 µmol/L), blocker of large conductance Ca2+-dependent K+ channels, significantly reduced SNP-induced inhibitory effects. In contrast, apamin (0.1 µmol/L), blocker of small conductance Ca2+-dependent K+ channels, was not able to affect the response to SNP. Ciclopiazonic acid (10 µmol/L) or thapsigargin (0.1 µmol/L), sarcoplasmatic reticulum Ca2+-ATPase inhibitors, decreased the SNP-inhibitory effects. Ryanodine (10 µmol/L), inhibitor of Ca2+...
NG-nitro-L-arginine methyl ester modulates intestinal secretion and motility produced by carbachol
European journal of pharmacology, 1994
The effects of the nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester, on carbachol-induced diarrhoea, fluid accumulation and motility changes were studied. Pretreatment of mice with NG-nitro-L-arginine methyl ester (1-25 mg/kg i.p.) and NG-nitro-L-arginine (2.5-50 mg/kg i.p.) but not NG-nitro-D-arginine methyl ester (25 mg/kg i.p.) prevented in a dose-related manner the carbachol (0.5 mg/kg i.p.)-induced diarrhoea in mice. L-Arginine (150-1500 mg/kg i.p.) administered to mice pretreated with NG-nitro-L-arginine methyl ester counteracted the antidiarrhoeal activity of NG-nitro-L-arginine methyl ester in a dose-related manner. Pretreatment of rats with NG-nitro-L-arginine methyl ester (2.5-25 mg/kg i.p.) decreased the intestinal fluid accumulation induced by carbachol in rats. NG-Nitro-D-arginine methyl ester was without effect. Intraperitoneal pretreatment of rats with NG-nitro-L-arginine methyl ester (2.5-25 mg/kg) reduced the increase in small intestinal trans...
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.
British Journal of Pharmacology, 1992
The present study was performed to investigate how blockade of the L-arginine/nitric oxide (NO) pathway influences the function of the lower urinary tract in vivo, as studied by cystometry in conscious rats and in vitro, in isolated muscle preparations from the rat detrusor and urethra. 2 L-N0-nitro arginine methyl ester (L-NAME), 10 and 20 mg kg-, administered intra-arterially, decreased micturition volume and bladder capacity, and increased spontaneous bladder contractions. D-NAME (20mgkg-') had no effect. No changes in the urodynamic parameters were recorded if L-NAME (20mgkg-') was administered in combination with L-arginine (200mgkg-'). 3 Cystometries performed after intra-arterial administration of sodium nitroprusside (SNP) (3mg kg-') and 3-morpholino-sydnonimin hydrochloride (SIN-1, 2mgkg-') showed a decrease in bladder capacity, micturition volume and threshold pressure. SIN-1, but not SNP, induced spontaneous bladder contractions. 4 Isolated precontracted urethral preparations responded to electrical stimulation with a frequencydependent tetrodotoxin-sensitive relaxation. L-NAME (10-4 M), but not D-NAME, reduced the maximal relaxation to 31 ± 8% (n = 8) of the response prior to drug administration. The inhibition induced by L-NAME was completely reversed by L-arginine (10-3 M). SNP (10-1 10-4 M), SIN-1 (10-6-3 x l0-4 M) and NO (10-5-10-3M; present in acidified solution of NaNO2), caused relaxation (93-100%) of urethral preparations. L-NAME did not affect these relaxations. 5 Detrusor strips contracted by carbachol or K' showed contractions in response to electrical stimulation, even when pretreated with a,p-methylene ATP and/or atropine. Small relaxations (14-41%) of detrusor strips were evoked by SNP (10-6-10-4M), SIN-1 (10-5-3 x 10-4M) and NO (10-5-10-3 M). Electrically (20 Hz) induced contractions of the detrusor muscle were unaffected by addition of L-NAME (10-6_10-4 M) or L-arginine (10-3 M). 6 The present results suggest that the L-arginine/NO pathway is of functional importance for the bladder outlet region, but that its role in the detrusor is questionable. They also suggest that the site of action of L-NAME for inducing bladder hyperactivity in the rat is the outlet region rather than the detrusor muscle.
Journal of neurogastroenterology and motility, 2018
The aim of present study is to estimate the effects of L. (MO) on visceral hypersensitivity (VH), defecation pattern and biochemical factors in 2 experimental models of irritable bowel syndrome (IBS) and the possible role of nitric oxide. Two individual models of IBS were induced in male Wistar-albino rats. In the acetic acid model, the animals were exposed to rectal distension and abdominal withdrawal reflex, and the defecation patterns were determined. In the restraint stress model, the colons of rats were removed and the levels of TNF-α, myeloperoxidase, lipid peroxidation, and antioxidant powers were determined. Rats had been treated with MO, L-NG-nitroarginine methyl ester (L-NAME), aminoguanidine (AG), MO + AG, or MO + L-NAME in the mentioned experimental models. Hypersensitive response to rectal distension and more stool defecation in control rats have been observed in comparison to shams. MO-300 significantly reduced VH and defecation frequency in comparison to controls. VH ...