Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats (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.
Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition
Gastroenterology, 1992
The effects of A7c-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) biosynthesis on the splanchnic and systemic circulation, were investigated in rats with cirrhosis induced by carbon tetrachloride. Portal hypertension in these rats was accompanied by decreased arterial blood pressure and peripheral vascular resistance as well as by splanchnic vasodilation with increased portal venous inflow and decreased splanchnic resistance. Intravenous bolus administration of L-NMMA (25 mg/kg) significantly increased systemic blood pressure and decreased cardiac output. L-NMMA also significantly increased systemic and splanchnic vascular resistance; whereas blood flow to the stomach, small intestine, colon, pancreas, mesentery, spleen, and kidney was decreased significantly. L-NMMA did not alter the portal pressure or portosystemic shunting in these cirrhotic rats, yet portal vascular resistance increased, suggesting effects on the intrahepatic and collateral circulation. Pretreatment with L-arginine (300 mg/kg) prevented the hemodynamic changes induced by L-NMMA. These findings support the concept that local excess formation of NO contributes to changes in splanchnic circulation associated with portal hypertension in cirrhosis.
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...
Physiological research / Academia Scientiarum Bohemoslovaca, 2007
N(G)-nitro-L-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the induction of NO-deficient hypertension. The aim of this study was to investigate the effect of chronic low-dose administration of L-NAME on NO production, vascular function and structure of the heart and selected arteries of rats. Adult male Wistar rats were treated with L-NAME in the dose of approximately 1.5 mg/kg/day in drinking water for 8 weeks. Basal blood pressure (BP) of rats (determined by tail-cuff) was 112+/-3 mm Hg. The low-dose administration of L-NAME significantly elevated BP measured on the third and sixth week of treatment vs. controls by approximately 9 % and 12 %, respectively. After this period, BP of L-NAME-treated rats returned to the control values. The relative left ventricular mass, heart fibrosis and collagen III/collagen I ratio were not affected by L-NAME. Similarly, there were no alterations in the cross-sectional area and wall thickn...
Mesenteric vasodilator responses in cirrhotic rats: A role for nitric oxide
Hepatology, 1996
mesenteric endothelial NO is unchanged or possibly di-The contribution of nitric oxide to mesenteric arterial minished. (HEPATOLOGY 1996;23:130-136.) vasodilator responses was investigated in the isolated perfused mesenteric arterial bed of cirrhotic rats (carbon tetrachloride/phenobarbitone; n Å 6). Age-matched (n Å 9) and phenobarbitone-treated rats (n Å 9)
Prolonged bleeding time in experimental cirrhosis: role of nitric oxide
Journal of Hepatology, 1999
Background~Aims: Nitric oxide is a powerful in vitro inhibitor of platelet adhesion and aggregation. Our aim was to investigate whether the in vivo inhibition of nitric oxide release shortens bleeding time, in rats with cirrhosis induced by chronic bile duct ligation. Methods: Mean arterial pressure and bleeding time were measured under basal conditions and 5, 15 and 30 min after administration of vehicle (0.9% saline) or an inhibitor of nitric oxide synthesis, Nw-nitro-Larginine (5 mg/kg, iv). Mean arterial pressure was measured with an intra-arterial catheter and bleeding time with a standardized Simplate device. Results: Cirrhotic rats showed a lower mean arterial pressure (116-+4 mmHg) and a prolonged bleeding time (177-+40 s) compared to control animals (133-+6 mmHg and 95-+12 S, respectively, p<0.01). In cirrhotic rats, Nw-nitro-L-arginine significantly in-creased mean arterial pressure (from 116_+5 to 141_+ 11 mmHg, p<0.05) and completely normalized bleeding time (from 170-+39 to 103-+21 S, p<0.05) 15 min after administration. Pretreatment with L-arginine (300 mg/kg, iv) prevented the hemodynamic and hemostatic changes induced by Nw-nitro-L-arginine. A trend to normalize platelet adhesion was observed in cirrhotic rats after the inhibition of nitric oxide production. In control animals, Nw-nitro-L-arginine increased mean arterial pressure, while no effect on bleeding time was observed. Conclusions: These findings support the concept that nitric oxide may be a mediator in the bleeding time abnormalities associated with experimental cirrhosis.
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 ...
Nitric oxide production in arterial vessels of cirrhotic rats
Hepatology, 1995
Indirect evidence exists implicating vascular nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. In the current study, a coincubation assay to estimate the vascular nitric oxide production was developed and the nitric oxide production by arterial segments of cirrhotic and control rats was assessed. In the assay, measurement of reporter monolayer cell-associated cGMP levels allows the influence of nitric oxide released by arterial segments to be determined. RFL-6 cells served as reporter cells. Nitric oxide production was determined in thoracic aorta and mesenteric arteries of 22 control rats, 10 cirrhotic rats without ascites, and 12 cirrhotic rats with ascites. Basal and bradykinin-stimulated (10 moYL) intracellular content of nitric oxidedependent cGMF' was significantly higher in RFL-6 cells coincubated with aortic segments of cirrhotic rats with (21.3 -c 3.6 pm01/105 cells, P < .05 and 44.7 2 7 . 0 pmol/105 cells, P < .025) and without ascites (15.3 5 3.0 pmoY105 cells, P < .05 and 43.2 i 7.6 pmol/105 cells, P < .05) than in those incubated with aortic segments of control rats (9.7 i 1.3 and 19.5 I 2.5 pmol/105 cells). RFLS cells exposed to bradykinin-stimulated mesenteric arterial segments of cirrhotic rats also showed increased cGMP content (ascitic: 2.73 ? 0.31 pmol/105 cells, P < .005; nonascitic: 2.58 ? 0.51 pmoY105 cells, P < .025) compared with cells exposed to control mesenteric arterial segments (1.28 t-0.15 pmol/105 cells). No differences between cirrhotic and control vessels were observed after endothelium denudation. These results indicate that basal and bradykinin-stimulated vascular nitric oxide production is higher in cirrhotic rats with and without ascites than in control rats in and that the endothelial lining is the site where vascular L-arginine nitric oxide pathway activation takes place in experimental cirrhosis. (HEPA-TOLOGY 1995; 21:554-560.) Patients and experimental animals with cirrhosis present a circulatory dysfunction characterized by arterial hypotension, marked decrease in peripheral vascular resistance, hypervolemia, and high cardiac output.'" The mechanism of these circulatory abnormalities is an arterial vasodilation, which predominantly takes place in the splanchnic circulation. Splanchnic arterial vasodilation is an important event in cirrhosis. By increasing portal venous inflow, it aggravates portal hypertension., On the other hand, arterial vasodilation is the most likely mechanism of the effective arterial hypovolemia, the activation of the renin-aldosterone and sympathetic nervous systems and antidiuretic hormone, and the impaired renal sodium and water excretion that characterize patients with advanced cirrhosis and ascites.5