Increased Nitric Oxide Synthesis and Inducible Nitric Oxide Synthase Expression in Patients with Alcoholic and Non-Alcoholic Liver Cirrhosis

1998 ◽  
Vol 94 (6) ◽  
pp. 637-643 ◽  
Author(s):  
A. Sánchez-Rodríguez ◽  
M. Criado ◽  
A. M. Rodríguez-López ◽  
A. Esteller ◽  
A. Martín De Arriba ◽  
...  

1. The synthesis and release of nitric oxide may play a role in the pathogenesis of peripheral vasodilatation and hyperdynamic circulation observed in liver cirrhosis. In this work, we analysed the synthesis of nitric oxide by the lympho-mononuclear cells of peripheral blood from patients with chronic alcoholic and non-alcoholic liver disease and we identified the isoform of nitric oxide synthase involved in the increased nitric oxide synthesis. 2. Patients were classified following clinical and histological criteria in non-alcoholic cirrhotic, alcoholic cirrhotic and non-cirrhotic chronic liver disease. We studied clinical and analytical characteristics, haemodynamic parameters and endotoxin levels in these patients. 3. Cirrhotic patients showed an increase of cardiac output and a decrease of peripheral vascular resistance. These patients had higher levels of plasma endotoxin than those observed in the control group. Nω-Nitro-l-arginine methyl ester (l-NAME)-inhibitable nitrite production from mononuclear lymphocyte cells was higher in patients than in the control group, the highest levels being in non-alcoholic cirrhotic patients, and the lowest levels in patients with non-cirrhotic alcoholic liver disease. 4. Immunocytochemistry studies revealed a positive immunoreactivity for the inducible isoform of nitric oxide synthase in lympho-mononuclear cells that was more evident in non-alcoholic than in alcoholic cirrhotic patients. By Northern blot, inducible nitric oxide synthase mRNA expression was observed only in lympho-mononuclear cells from non-alcoholic cirrhotic patients. 5. Our patients show a correlation between nitric oxide synthesis, endotoxin levels and haemodynamic parameters. 6. These findings indicate that lympho-mononuclear cell stimulation may play a role in elevated nitric oxide production in hepatic cirrhosis. Thus, this increased nitric oxide synthesis could be implicated in the pathogenesis of the haemodynamic disturbances frequently found in cirrhotic patients. This increase seems to be induced, at least in part, by activation of an inducible isoform of nitric oxide synthase.

2005 ◽  
Vol 288 (6) ◽  
pp. E1252-E1257 ◽  
Author(s):  
Isabel Rodríguez-Gómez ◽  
Rosemary Wangensteen ◽  
Juan Manuel Moreno ◽  
Virginia Chamorro ◽  
Antonio Osuna ◽  
...  

We hypothesized that nitric oxide generated by inducible nitric oxide synthase (iNOS) may contribute to the homeostatic role of this agent in hyperthyroidism and may, therefore, participate in long-term control of blood pressure (BP). The effects of chronic iNOS inhibition by oral aminoguanidine (AG) administration on BP and morphological and renal variables in hyperthyroid rats were analyzed. The following four groups ( n = 8 each) of male Wistar rats were used: control group and groups treated with AG (50 mg·kg−1·day−1, via drinking water), thyroxine (T4, 50 μg·rat−1·day−1), or AG + T4. All treatments were maintained for 3 wk. Tail systolic BP and heart rate (HR) were recorded weekly. Finally, we measured BP (mmHg) and HR in conscious rats and morphological, plasma, and renal variables. T4 administration produced a small BP (125 ± 2, P < 0.05) increase vs. control (115 ± 2) rats. AG administration to normal rats did not modify BP (109 ± 3) or any other hemodynamic variable. However, coadministration of T4 and AG produced a marked increase in BP (140 ± 3, P < 0.01 vs. T4). Pulse pressure and HR were increased in both T4- and T4 + AG -treated groups without differences between them. Plasma NOx (μmol/l) were increased in the T4 group (10.02 ± 0.15, P < 0.05 vs. controls 6.1 ± 0.10), and AG reduced this variable in T4-treated rats (6.81 ± 0.14, P < 0.05 vs. T4) but not in normal rats (5.78 ± 0.20). Renal and ventricular hypertrophy and proteinuria of hyperthyroid rats were unaffected by AG treatment. In conclusion, the results of the present paper indicate that iNOS activity may counterbalance the prohypertensive effects of T4.


2013 ◽  
Vol 16 (3) ◽  
pp. 443-451 ◽  
Author(s):  
W. Barański ◽  
J. Kaleczyc ◽  
S. Zduńczyk ◽  
W. Podlasz ◽  
E. Długołęcka-Malinowska ◽  
...  

Abstract The expression of CD14+ macrophages, CD4+, CD8+ lymphocytes and mRNA of inducible nitric oxide synthase (iNOS) was investigated in the endometrium of repeat breeders with subclinical endometritis [experimental group (EXP), n = 10] and healthy [control group (CTRL), n = 10] cows. The cows were selected on the basis of repeat breeding (3 unsuccessful inseminations), clinical and cytological examinations (> 10% polymorphonuclear neutrophils in uterine smears obtained by cytobrush). From all the cows endometrial biopsies were collected and the presence of CD14+, CD4+ and CD8+ cells in the endometrium was evaluated immunohistochemically using semi quantitative counting method. The mRNA expression of iNOS was determined using reverse transcription-PCR. In general, there were no significant differences between EXP and CTRL groups in the expression of CD4+ and CD8 + lymphocytes in all endometrial structures. In contrast, we observed a higher number of CD14+ macrophages in repeat breeding group compared to the control cows, however, this difference was slightly pronounced. CD14+ cells were detectable only in the stratum compactum and stratum spongiosum. The statistically significant (p ≤ 0.05) higher expression of iNOS mRNA was measured in the cows with subclinical endometritis compared to the healthy animals. Our results suggest that the increased expression of CD14+ macrophages and iNOS mRNA may be associated with embryonal mortality in repeat breeding cows with subclinical endometritis.


Reproduction ◽  
2001 ◽  
pp. 403-407 ◽  
Author(s):  
M Farina ◽  
ML Ribeiro ◽  
A Franchi

The conversion of [14C]arginine into [14C]citrulline as an indicator of nitric oxide synthesis was studied in uteri isolated from rats on different days of gestation, after labour and during dioestrus. Nitric oxide synthesis was present in uterine tissues isolated at each stage of gestation and also in tissues collected during dioestrus and after labour. Expression of neuronal nitric oxide synthase was not detectable at any of the stages studied. Endothelial nitric oxide synthase was present at all the stages studied, but there was a significant increase on day 13 of gestation and a decrease thereafter, with the lowest expression recorded on the day after labour. Inducible nitric oxide synthase expression in rat uteri increased substantially during pregnancy, with the highest expression on day 13 of gestation; expression decreased at term and after labour. The changes in expression of inducible nitric oxide synthase were coincident with the changes in nitric oxide synthase activity in uteri treated with aminoguanidine. Thus, these findings indicate that an increase in expression of inducible nitric oxide synthase in the uterus may be important for maintenance of uterine quiescence during pregnancy and its decrease near the time of labour could have an effect on the start of uterine contractility.


2004 ◽  
Vol 279 (53) ◽  
pp. 55682-55689 ◽  
Author(s):  
Inmaculada Navarro-Lérida ◽  
Maria Martha Corvi ◽  
Alberto Álvarez Barrientos ◽  
Francisco Gavilanes ◽  
Luc Gérard Berthiaume ◽  
...  

Hepatology ◽  
1999 ◽  
Vol 30 (3) ◽  
pp. 670-676 ◽  
Author(s):  
Wladimiro Jiménez ◽  
Josefa Ros ◽  
Manuel Morales-Ruiz ◽  
Miguel Navasa ◽  
Manuel Solé ◽  
...  

2011 ◽  
Vol 183-185 ◽  
pp. 2207-2210
Author(s):  
Li Fang Sun ◽  
Bing Quan Zhang ◽  
Na Zhang ◽  
Yan Ying Wang ◽  
Jing Yu

The aim of this study was to define that the expression of inducible nitric oxide synthase (iNOS)in cell blocks from ascites was a certain value to evaluate hepatopulmonary syndrome(HPS). iNOS can stimulate the liver and lung to produce excess NO. Excessive production of NO can cause pulmonary vasodilatation and impaire arterial oxygenation. HPS is characterized by shortness of breath and hypoxemia caused by impaired arterial oxygenation due to pulmonary microvascular dilatation in patients with liver disease or PTH. Therefore.the positive rates of iNOS was a certain value to evaluate the conditions of HPS.


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