NG-nitro-L-arginine methyl ester modulates intestinal secretion and motility produced by carbachol (original) (raw)
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Experimental and Toxicologic Pathology, 2003
Inflammatory bowel disease (IBD) has been associated with an increased generation of nitric oxide (NO). Different authors have shown that NO in IBD can be either harmful or protective. The aim of this study was to investigate the efficiency of intrarectal (IR) and intraperitoneal (IP) application of N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific nitric oxide synthase inhibitor, in experimental acute colitis in the rats. Acute colitis was induced in rats by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. Twenty-eight rats were divided into four groups. L-NAME (50 mg/kg/day) was administered IP (Group 1) and IR (Group 2) for 7 days following the day when colitis was induced. Group 3 rats were not given any treatment after induction of colitis. Control group rats were given saline solution IR instead of TNBS. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The severity of colitis was assessed by microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation. Rectal tissue myeloperoxidase (MPO) activity and serum-rectal tissue nitrite levels were measured. Serum and rectal tissue nitrite levels increased in Group 3 rats. Both IP and IR L-NAME treatment significantly reduced serum and rectal tissue nitrite levels, but no effect on MPO activity and histologic damage score was observed. Under the present conditions we concluded IR and IP L-NAME treatment, applied at the dosage of 50 mg/kg/day, does not have any protective effect on the colonic injury.
Methyl Ester Modulates Intestinal Secretion and Motility Produced by Carbachol
European Journal of Pharmacology, 1994
The effects of the nitric oxide (NO) synthesis inhibitor, N°-nitro-L-arginine methyl ester, on carbachol-induced diarrhoea, fluid accumulation and motility changes were studied. Pretreatment of mice with N°-nitro-L-arginine methyl ester (1-25 mg/kg i.p.) and N°-nitro-L-arginine (2.5-50 mg/kg i.p.) but not N°-nitro-D-arginine methyl ester (25 mg/kg i.p.) prevented in a dose-related manner the carbaehol (0.5 mg/kg i.p.)-induced diarrhoea in mice. L-Arginine (150-1500 mg/kg i.p.) administered to mice pretreated with N°-nitro-L-arginine methyl ester counteracted the antidiarrhoeal activity of N°-nitro-L-arginine methyl ester in a dose-related manner. Pretreatment of rats with N°-nitro-L-arginine methyl ester (2.5-25 mg/kg i.p.) decreased the intestinal fluid accumulation induced by carbachol in rats. NG-Nitro-I>-arginine methyl ester was without effect. Intraperitoneal pretreatment of rats with N°-nitro-L-arginine methyl ester (2.5-25 mg/kg) reduced the increase in small intestinal transit induced by carbachol. N°-nitro-L-arginine methyl ester had no effect. These results provide evidence that nitric oxide may play a role in diarrhoea, intraluminal fluid accumulation and motility changes induced by carbachol.
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
Biological & Pharmaceutical Bulletin, 2011
Nitric oxide synthase (NOS) inhibitors alleviate the adverse effects of nitric oxide (NO) overproduction that occurs during peritonitis, a clinical condition that is accompanied by arginine deficiency. However, the variations in the disease severity and the dosage, route, and period of NOS inhibitor administration are debatable. Therefore, we investigated the dose effects of chronically infused NOS inhibitor, N G -nitro-L-arginine methyl ester (L-NAME) on the anabolism, inflammatory responses, and arginine metabolism in parenterally fed rats with cecal puncture-induced subacute peritonitis. Male Wistar rats were divided into 4 groups and were administered total parenteral nutrition solutions with 0, 5 (low dose), 25 (medium dose), or 50 (high dose) mg · kg ؊ ؊1 ·d ؊ ؊1 of L-NAME for 7 d. Sham-operated rats administered total parenteral nutrition solution and normal healthy rats fed chow diet were also included. Our results showed that parenteral infusion significantly decreased body weight gain and plasma citrulline concentrations. In rats with subacute peritonitis, the parenteral infusion-induced increases in circulating white blood cells and NO were significantly decreased, whereas the decrease in serum albumin levels was significantly increased. Rats with subacute peritonitis that were administered chronic infusion of L-NAME had a significantly reduced nitrogen balance. In addition, rats administered the medium dose of L-NAME had significantly increased plasma arginine, ornithine, glutamate, and proline. In conclusion, chronic infusion of NOS inhibitors may not alter systemic NO homeostasis and inflammatory response but may facilitate the production of arginine-associated amino acids and nitrogen excretion in cases of subacute peritonitis.
European Journal of Pharmacology, 1999
In this study the effect of nitric oxide NO synthesis inhibition on ethanol-induced gastric damage was evaluated in bile duct-ligated, Ž. G sham-operated and unoperated rats. The animals were injected intraperitoneally with saline, L-arginine 200 mgrkg or N-nitro-L-arginine Ž. methylester L-NAME in doses of 5, 15 and 30 mgrkg, 30 min before ethanol administration. The animals were killed 1 h after ethanol administration and their stomachs were removed for measurement of gastric mucosal damage. The results showed that L-NAME significantly enhanced the development of gastric mucosal lesions in sham-operated and unoperated rats, while in bile duct-ligated animals, L-NAME decreased and L-arginine enhanced the potentiation of ethanol-induced gastric mucosal damage. The plasma level of nitrite and nitrate was also measured and was significantly higher in bile duct-ligated rats than in control groups. The results suggest that inhibition of NO synthase with L-NAME has different effects on ethanol-induced gastric damage in cholestatic groups and in normal rats and that these effects can be explained by overproduction of NO in bile duct-ligated animals.
New Issues about Nitric Oxide and its Effects on the Gastrointestinal Tract
Current Pharmaceutical Design, 2001
Over the last years the important role of nitric oxide (NO) as endogenous modulator of numerous physiological functions has been shown. NO is involved in the regulation of blood flow, maintenance of vascular tone, control of platelet aggregation, and modulation of the activity of the mastocytes. It also plays a key role as neurotransmitter in the central and peripheric nervous system (non adrenergic non colinergic, NANC, neurons), in the nervous control of the cerebral blood flow and in the neuroendocrine regulation or synaptic plasticity. However, NO shows a dual behavior: at physiological concentrations, released through the constitutive synthase (cNOS), it regulates house-keeping functions, whereas its overproduction by the inducible isoenzyme (iNOS) exhibits cytotoxic activity because interacting with reactive species producing peroxinitrites (ONOO • ) and other compounds, which are highly damaging for the tissues.
Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats
2000
AIM: To investigate the effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats. METHODS: Rats with cirrhosis induced by carbon tetrachloride were randomly divided into two groups, one(n=13) receiving 0.5mg·kg -1 per day of N-G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, for 10 days, whereas the other group (n=13) and control (n=10) rats were