Interaction between prostanoids and nitric oxide in the control of tubular function in rats with chronic bile duct ligation

1999 ◽  
Vol 77 (2) ◽  
pp. 111-117 ◽  
Author(s):  
Manuela Criado ◽  
Olga Flores ◽  
Froilán Hidalgo ◽  
José M López-Novoa ◽  
Angel Sánchez-Rodríguez
Keyword(s):  
Nitric Oxide ◽  
Mean Arterial Pressure ◽  
Bile Duct ◽  
Methyl Ester ◽  
Arterial Pressure ◽  
Bile Duct Ligation ◽  
Prostaglandin E ◽  
Duct Ligation ◽  
Pressure Natriuresis ◽  
Oxide Synthase

Recent work indicates that both nitric oxide and cyclooxygenase products play an important role in the renal alterations of liver cirrhosis, although the interactions between them have not been completely established. The purpose of this study was to assess the effect of simultaneous blockade of nitric oxide synthase and cyclooxygenase in rats with chronic bile duct ligation and in control, sham-operated rats. Compared with control rats, chronic bile duct ligation rats, 23-25 days after surgery, showed a decreased mean arterial pressure, natriuresis, and kaliuresis, without differences in glomerular filtration rate, and an increased urinary nitrite excretion. Nitric oxide synthesis inhibition by administration of NG-nitro-L-arginine methyl ester induced, in control rats, an increase in mean arterial pressure, without significant changes in natriuresis or glomerular filtration rate. In chronic bile duct ligation rats, NG-nitro-L-arginine methyl ester induced an increase in mean arterial pressure, natriuresis, and kaliuresis, together with a reduction in urinary nitrite excretion and an increase in prostaglandin E2 excretion. Cyclooxygenase inhibition with indomethacin induced in both experimental groups a marked inhibition in urinary prostaglandin E2 excretion without significant changes in Na+ or K+ excretion, and a significant increase in urinary nitrite excretion in control rats. NG-Nitro-L-arginine methyl ester in addition to indomethacin prevented the indomethacin-induced increase in nitrite excretion and dramatically reduced sodium excretion in both experimental groups. Thus, the present study suggests that both nitric oxide and cyclooxygenase products interact in the control of urinary sodium excretion and that each system is activated in the absence of the other one.Key words: kidney, biliary cirrhosis, nitric oxide synthase, cyclooxygenase.

Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation

1999 ◽  
Vol 96 (3) ◽  
pp. 297-305 ◽  
Author(s):  
Paula MAYORAL ◽  
Manuela CRIADO ◽  
Froilan HIDALGO ◽  
Olga FLORES ◽  
Miguel A. ARÉVALO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Nitric Oxide Synthase ◽  
Hepatic Fibrosis ◽  
Bile Duct Ligation ◽  
Common Bile Duct Ligation ◽  
Western Blots ◽  
Circulatory Effects ◽  
Duct Ligation ◽  
Oxide Synthase

Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG-nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct ligated rats. They also support the hypothesis of a dual role for nitric oxide; one beneficial, mediated by its circulatory effects, and the second negative, through its local toxic effects.

scholarly journals The Impact of a Nitric Oxide Synthase Inhibitor (L-NAME) on Ischemia–Reperfusion Injury of Cholestatic Livers by Pringle Maneuver and Liver Resection after Bile Duct Ligation in Rats

2019 ◽  
Vol 20 (9) ◽  
pp. 2114 ◽  
Author(s):  
Junji Iwasaki ◽  
Mamdouh Afify ◽  
Christian Bleilevens ◽  
Uwe Klinge ◽  
Ralf Weiskirchen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Resection ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pringle Maneuver ◽  
Endothelial Lining ◽  
Duct Ligation ◽  
Oxide Synthase

The Pringle maneuver (PM) has been widely used to control blood loss during liver resection. However, hepatic inflow occlusion can also result in hepatic ischemia–reperfusion injury (IRI), especially in patients with a cholestatic, fibrotic, or cirrhotic liver. Here we investigate a nitric oxide synthase (NOS) inhibitor N-Nitroarginine methyl ester (L-NAME) on IRI after the PM and partial hepatectomy of cholestatic livers induced by bile duct ligation (BDL) in rats. Control group (non-BDL/no treatment), BDL + T group (BDL/L-NAME treatment) and BDL group (BDL/no treatment) were analyzed. Cholestasis was induced by BDL in the L-NAME and BDL group and a 50% partial hepatectomy with PM was performed. L-NAME was injected before PM in the BDL + T group. Hepatocellular damage, portal venous flow, microcirculation, endothelial lining, and eNOS, iNOS, interleukin (IL)-6, and transforming growth factor-β (TGF-β) were evaluated. Microcirculation of the liver in the BDL + T group tended to be higher. Liver damage and apoptotic index were significantly lower and Ki-67 labeling index was higher in the BDL + T group while iNOS and TGF-β expression was decreased. This was corroborated by a better preserved endothelial lining. L-NAME attenuated IRI following PM and improved proliferation/regeneration of cholestatic livers. These positive effects were considered as the result of improved hepatic microcirculation, prevention of iNOS formation, and TGF-β mRNA upregulation.

Abstract 316: Effects of Inhibiting of Inducible Nitric Oxide Synthase in the Pathophysiology of Experimental Preeclampsia

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Lorena M Amaral ◽  
Ana Carolina T Palei ◽  
Lucas C Pinheiro ◽  
Jonas T Sertorio ◽  
Danielle A Guimaraes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The pathophysiology of preeclampsia (PE) is not entirely known. However, increased oxidative stress possibly leading to impaired nitric oxide activity has been implicated in the critical condition. Increased oxidative stress with increased levels of highly reactive species including superoxide may generate peroxynitrite. We examined the role of inducible nitric oxide synthase (iNOS) and oxidative stress in the reduced uterine perfusion pressure (RUPP) preeclampsia experimental model. METHODS: RUPP was induced in wistar rats. Pregnant rats in the RUPP group had their aortic artery clipped at day 14 of gestation. After a midline incision, a silver clip (0.203 mm) was placed around the aorta above the iliac bifurcation; silver clips (0.100 mm) were also placed on branches of both the right and left ovarian arteries that supply the uterus. Sham-operated (pregnant control rats) and RUPP rats were treated with oral vehicle or 1 mg/kg/day 1400W (iNOS inhibitor) for 5 days. Mean arterial pressure (MAP) and plasma levels of thiobarbituric acid-reactive species (TBARS) and total radical-trapping antioxidant potential (TRAP) were measured determined. Aortic iNOS expression (Western blotting) and reactive oxygen species (ROS; assessed by fluorescence microscopy with dihydroethidium-DHE) were measured. We found increased mean arterial pressure in RUPP compared with pregnant control rats (MAP= 128±1 vs. 100±1.8 mmHg, respectively; P<0.05) and 1400W exerted antihypertensive effects (MAP= 114±2 vs.128±1 mmHg in RUPP treated and untreated rats, respectively; P<0.05). Higher reactive oxygen species (ROS) concentrations were found in RUPP compared with pregnant control rats (7.1±0.5 vs. 5.1±0.5 arbitrary units (A.U.), respectively; P<0.05) and 1400W decreased ROS production to 5.8±0.02 A.U. in RUPP treated rats, P<0.05. In addition, 1400W attenuated iNOS expression in RUPP rats (0.29±0.02 vs. 0.55±0.8 A.U. in RUPP treated and untreated rats, respectively; P<0.01) and had no effects on plasma TBARS and TRAP levels. Our results suggest that 1400w exerts antihypertensive effects in the RUPP model and suppresses ROS formation. Supported by FAPESP,Cnpq.

Regulation of inducible nitric oxide synthase and nitric oxide during hepatic injury and fibrogenesis

1997 ◽  
Vol 273 (1) ◽  
pp. G124-G130 ◽  
Author(s):  
D. C. Rockey ◽  
J. J. Chung
Keyword(s):  
Nitric Oxide ◽  
Carbon Tetrachloride ◽  
Bile Duct ◽  
Kupffer Cells ◽  
Hepatic Injury ◽  
Bile Duct Ligation ◽  
Inos Mrna ◽  
No Production ◽  
Nonparenchymal Cells ◽  
Duct Ligation

Nitric oxide (NO) production via inducible NO synthase (iNOS) is prominent in the liver after stimulation with cytokines and/or lipopolysaccharide. The aim of this study was to investigate the production of NO via iNOS in specific liver cell populations during toxin-mediated and obstructive hepatic injury and fibrogenesis. After a single dose of carbon tetrachloride, iNOS mRNA and nitrite (a metabolic product of NO) were detected only in Kupffer cells. They were not detectable in any cell type after recurrent administration of carbon tetrachloride, including in animals with far advanced cirrhosis (i.e., portal hypertension and/or ascites). After bile duct ligation, a mechanistically different form of liver injury and fibrogenesis, iNOS mRNA and nitrite were identified in all nonparenchymal cells but not in hepatocytes. Twenty-four hours after bile duct ligation, iNOS mRNA and NO production were greatest in Kupffer cells, but after prolonged bile duct ligation, iNOS was found predominantly in sinusoidal endothelial cells. These data indicate that iNOS expression varies temporally and spatially in the liver after injury and also varies with the type of insult.

495 Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 398-398
Author(s):  
X ZHANG ◽  
Y KATSUTA ◽  
T AKIMOTO ◽  
M OHSUGA ◽  
Y KATO ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Duct Ligation ◽  
Vascular Dilatation

Influence of nitric oxide on the hemodynamic response to hemorrhage in conscious rabbits

1995 ◽  
Vol 268 (1) ◽  
pp. R171-R182 ◽  
Author(s):  
M. A. Koch ◽  
E. M. Hasser ◽  
J. C. Schadt
Keyword(s):  
Nitric Oxide ◽  
Mean Arterial Pressure ◽  
Nitric Oxide Synthase ◽  
Arterial Pressure ◽  
Hemodynamic Response ◽  
Nitric Oxide Synthase Inhibitor ◽  
Acute Hemorrhage ◽  
Conscious Rabbits ◽  
Synthase Inhibitor ◽  
Oxide Synthase

We investigated the role of nitric oxide, an endothelium-derived relaxing factor, in the hemodynamic response to acute hemorrhage in conscious rabbits. Chronically instrumented rabbits were treated with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) or vehicle and hemorrhaged until mean arterial pressure fell below 40 mmHg. Control animals were treated with L-NAME or vehicle but not subjected to hemorrhage. L-NAME increased mean arterial pressure and decreased heart rate in control animals. Hindquarters and mesenteric blood flow velocity and conductance were reduced by L-NAME. Nitric oxide synthase inhibition also produced significant changes in the hemodynamic response to hypotensive hemorrhage. Mean arterial pressure was higher and regional vascular conductances were lower throughout hemorrhage and during recovery. L-NAME treatment significantly (but in some cases, subtly) altered the characteristic pattern of changes in vascular conductance associated with acute hypotensive hemorrhage and recovery. Similar experiments with other arginine analogues or phenylephrine infusion showed that L-NAME's effects during hemorrhage were due to nitric oxide synthase inhibition. We conclude that nitric oxide plays a role in the hemodynamic response to acute hemorrhage in the rabbit and is essential for the full expression of the vasodilation associated with hypotensive hemorrhage.

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