Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or ...Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.展开更多
Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolyt...Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.展开更多
AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic rats.METHODS Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15...AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic rats.METHODS Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P < 0.05) in PPVL and further enhanced(P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.展开更多
Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separatio...Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separation of ADMA and SDMA was successfully performed using a silica column with optimized elution, or mobile phase, of 10 mM ammonium acetate buffer H2O/methanol/acetonitrile (20/30/45, v/v) at pH 4. The calibration ranges were 0.50 – 50.0 μg●mL-1, and good linearities were obtained for all compounds ( γ > 0.99). The intra- and inter-assay accuracies with recoveries and precisions at three concentration levels (i.e. 1.00, 5.00 and 25.0 μg●mL-1) were better than 86.9% and 7.36%, respectively. The analytical performance of the method was evaluated by determination of compounds in plasma, urine and tissues from male BALBc/J mice. For the first time, we were able to characterize the distribution of ADMA, SDMA and ADMA/SDMA in plasma, urine, brain, heart, kidneys, liver, lungs, pancreas and spleen. Additionally, we demonstrated that the ADMA/SDMA ratio in the brain was approximately 10-fold lower than all the other biological samples. Only 10 μL of plasma, 1 μL of urine and about 25 mg of tissues were required. These results suggest that the developed methodology was useful in ADMA and SDMA determination within biological samples.展开更多
Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is ...Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is a major complicating factor and key cause of mortality in this population. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy result in arrest of the lung development leading to BPD with PH. Early recognition of PH in infants with these risk factors is important for optimal management. We tested the hypothesis that asymmetric dimethylarginine, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone. The Aim: The aim of the current study was to measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary dysplasia, to evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia, to correlate between plasma ADMA & arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level. Methods: A case-control study was carried out of ninety (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and Alzhraa University hospital during the period from October 2015 to March 2018. Neonates were divided into 2 groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates. Patient with BPD only (Control group): It included 45 neonates with BPD without PH. These 45 neonates were divided as 22 preterm neonates and 23 full term neonates. Laboratory work was done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels & arginine levels were measured using competitive enzyme linked immune-assay (ELISA). Results: Patients with both BPD and PH had greater plasma levels of ADMA than patients with BPD alone (P value 0.000). ADMA level > 186 ng/dl can predict development of PH in patient with BPD with sensitivity 100% and specify 100%. Preterm neonates with BPD had greater level of ADMA than full term neonates (P value 0.002). There was no statically significance difference between level of ADMA if withdrawn before or after 28 days of age (range of age at time of sampling in our study was 23 - 40 days) (P value 0.878), even ADMA level increased above the cut point early in the disease before we screened some cases by ECHO. There was no statically significance difference between level of arginine in cases and control groups with P value 0.530. The plasma arginine-to-ADMA ratio was lower in cases than in controls suggesting a greater likelihood of inhibition of nitric oxide production in patients with both BPD and PH than in patients with BPD alone (P value 0.000). ADMA level can predict severity of pulmonary hypertension in patient with BPD, as it was positively correlated with the grade of pulmonary hypertension (P value 0.006). ADMA level is higher in neonates with BPD and PH who died than those who survived;it can predict death in neonates with BPD &PH at cut off point > 643 ng/dl. Conclusion: ADMA increased in newborn infants with BPD, who developed PH. ADMA may have diagnostic and prognostic values. ADMA level was higher in preterm neonates than full term neonates and its level was correlated positively with severity of PH. ADMA levels were significant higher in infants with BPD with PH who died later than those who survived. There was no statically significance difference between levels of ADMA, whether it was drawn before or after 28 days of age (range 23 - 40 days). Echocardiographic screening and ADMA measurement could help in prevention of PH, diagnosis and early treatment of newborn infants suffering from BPD.展开更多
Nitric oxide(NO),a multifunctional endogenous gas molecule,is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase.NO,an important gas signaling molecule,is a gastric mucosa prote...Nitric oxide(NO),a multifunctional endogenous gas molecule,is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase.NO,an important gas signaling molecule,is a gastric mucosa protective factor that contributes significantly to maintain normal gastric mucosa integrity.NO increases gastric mucosa blood flow,regulates the secretion of mucus and bicarbonate,and inhibits the secretion of gastric juice.Asymmetric dimethylarginine(ADMA) has been identified as the major endogenous inhibitor of nitric oxide synthase.The function of ADMA is to decrease NO production via inhibiting nitric oxide synthase activity.Besides inhibiting NO synthesis,ADMA also directly induces oxidative stress and cell apoptosis,and participates in inflammation reaction.Its systemic accumulation was observed in conjunction with several cardiovascular and metabolic diseases.ADMA also mediates gastric ulcer injury induced by ethanol,stress,helicobacter pylori and indomethacin.The mechanism of ADMA directly producing adverse effect in gastric mucosa is incompletely understood.It is widely accepted that NO bioavailability decrease is the majority reason.Promotion of apoptosis and aggravation of inflammation may be other important mechanisms of ADMA-induced gastric injury.ADMA might be a novel clinical and experimental biomarker related to gastric mucosa disorder.Although therapeutic tool targeting to ADMA is available in multiple cardiovascular diseases,it is unknown in gastrointestinal disease.The strategy to inhibit ADMA is beneficial to gastric ulcer induced by ethanol in rats.Thus,ADMA might be a candidate of therapeutic target in gastric mucosa damage.展开更多
AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt(TIPS).METHODS:To determine arginine,asymmetric dimethylarginine(ADMA),symmetric...AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt(TIPS).METHODS:To determine arginine,asymmetric dimethylarginine(ADMA),symmetric dimethylarginine(SDMA),and nitric oxide(NO) plasma levels,blood samples were collected from the superior cava,hepatic,and portal vein just before,directly after,and 3 mo after TIPS-placement.RESULTS:A significant increase in the arginine/ADMA ratio after TIPS placement was shown.Moreover,TIPS placement enhanced renal function and thereby decreased systemic SDMA levels.In patients with renal dysfunction before TIPS placement,both the arginine/ADMA ratio and creatinine clearance rate increased significantly,while this was not the case in patients with normal renal function before TIPS placement.Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured.CONCLUSION:The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability.In addition,this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase(DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.展开更多
文摘Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.
文摘Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.
基金Supported by Consellería de Sanidad of the Generalitat Valenciana,No.AP-052/08
文摘AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic rats.METHODS Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P < 0.05) in PPVL and further enhanced(P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.
文摘Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separation of ADMA and SDMA was successfully performed using a silica column with optimized elution, or mobile phase, of 10 mM ammonium acetate buffer H2O/methanol/acetonitrile (20/30/45, v/v) at pH 4. The calibration ranges were 0.50 – 50.0 μg●mL-1, and good linearities were obtained for all compounds ( γ > 0.99). The intra- and inter-assay accuracies with recoveries and precisions at three concentration levels (i.e. 1.00, 5.00 and 25.0 μg●mL-1) were better than 86.9% and 7.36%, respectively. The analytical performance of the method was evaluated by determination of compounds in plasma, urine and tissues from male BALBc/J mice. For the first time, we were able to characterize the distribution of ADMA, SDMA and ADMA/SDMA in plasma, urine, brain, heart, kidneys, liver, lungs, pancreas and spleen. Additionally, we demonstrated that the ADMA/SDMA ratio in the brain was approximately 10-fold lower than all the other biological samples. Only 10 μL of plasma, 1 μL of urine and about 25 mg of tissues were required. These results suggest that the developed methodology was useful in ADMA and SDMA determination within biological samples.
文摘Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is a major complicating factor and key cause of mortality in this population. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy result in arrest of the lung development leading to BPD with PH. Early recognition of PH in infants with these risk factors is important for optimal management. We tested the hypothesis that asymmetric dimethylarginine, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone. The Aim: The aim of the current study was to measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary dysplasia, to evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia, to correlate between plasma ADMA & arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level. Methods: A case-control study was carried out of ninety (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and Alzhraa University hospital during the period from October 2015 to March 2018. Neonates were divided into 2 groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates. Patient with BPD only (Control group): It included 45 neonates with BPD without PH. These 45 neonates were divided as 22 preterm neonates and 23 full term neonates. Laboratory work was done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels & arginine levels were measured using competitive enzyme linked immune-assay (ELISA). Results: Patients with both BPD and PH had greater plasma levels of ADMA than patients with BPD alone (P value 0.000). ADMA level > 186 ng/dl can predict development of PH in patient with BPD with sensitivity 100% and specify 100%. Preterm neonates with BPD had greater level of ADMA than full term neonates (P value 0.002). There was no statically significance difference between level of ADMA if withdrawn before or after 28 days of age (range of age at time of sampling in our study was 23 - 40 days) (P value 0.878), even ADMA level increased above the cut point early in the disease before we screened some cases by ECHO. There was no statically significance difference between level of arginine in cases and control groups with P value 0.530. The plasma arginine-to-ADMA ratio was lower in cases than in controls suggesting a greater likelihood of inhibition of nitric oxide production in patients with both BPD and PH than in patients with BPD alone (P value 0.000). ADMA level can predict severity of pulmonary hypertension in patient with BPD, as it was positively correlated with the grade of pulmonary hypertension (P value 0.006). ADMA level is higher in neonates with BPD and PH who died than those who survived;it can predict death in neonates with BPD &PH at cut off point > 643 ng/dl. Conclusion: ADMA increased in newborn infants with BPD, who developed PH. ADMA may have diagnostic and prognostic values. ADMA level was higher in preterm neonates than full term neonates and its level was correlated positively with severity of PH. ADMA levels were significant higher in infants with BPD with PH who died later than those who survived. There was no statically significance difference between levels of ADMA, whether it was drawn before or after 28 days of age (range 23 - 40 days). Echocardiographic screening and ADMA measurement could help in prevention of PH, diagnosis and early treatment of newborn infants suffering from BPD.
文摘Nitric oxide(NO),a multifunctional endogenous gas molecule,is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase.NO,an important gas signaling molecule,is a gastric mucosa protective factor that contributes significantly to maintain normal gastric mucosa integrity.NO increases gastric mucosa blood flow,regulates the secretion of mucus and bicarbonate,and inhibits the secretion of gastric juice.Asymmetric dimethylarginine(ADMA) has been identified as the major endogenous inhibitor of nitric oxide synthase.The function of ADMA is to decrease NO production via inhibiting nitric oxide synthase activity.Besides inhibiting NO synthesis,ADMA also directly induces oxidative stress and cell apoptosis,and participates in inflammation reaction.Its systemic accumulation was observed in conjunction with several cardiovascular and metabolic diseases.ADMA also mediates gastric ulcer injury induced by ethanol,stress,helicobacter pylori and indomethacin.The mechanism of ADMA directly producing adverse effect in gastric mucosa is incompletely understood.It is widely accepted that NO bioavailability decrease is the majority reason.Promotion of apoptosis and aggravation of inflammation may be other important mechanisms of ADMA-induced gastric injury.ADMA might be a novel clinical and experimental biomarker related to gastric mucosa disorder.Although therapeutic tool targeting to ADMA is available in multiple cardiovascular diseases,it is unknown in gastrointestinal disease.The strategy to inhibit ADMA is beneficial to gastric ulcer induced by ethanol in rats.Thus,ADMA might be a candidate of therapeutic target in gastric mucosa damage.
文摘AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt(TIPS).METHODS:To determine arginine,asymmetric dimethylarginine(ADMA),symmetric dimethylarginine(SDMA),and nitric oxide(NO) plasma levels,blood samples were collected from the superior cava,hepatic,and portal vein just before,directly after,and 3 mo after TIPS-placement.RESULTS:A significant increase in the arginine/ADMA ratio after TIPS placement was shown.Moreover,TIPS placement enhanced renal function and thereby decreased systemic SDMA levels.In patients with renal dysfunction before TIPS placement,both the arginine/ADMA ratio and creatinine clearance rate increased significantly,while this was not the case in patients with normal renal function before TIPS placement.Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured.CONCLUSION:The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability.In addition,this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase(DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.
