dimethylarginine and Body-Weight

Nitric oxide (NO) is an important mediator involved in vascular homeostasis. Changes in NO level are considered to be associated with obesity and its clinical consequences. Previous studies on NO levels in obese children provided inconclusive results, so this issue requires clarification.. One of the main goals of this study was to assess whether childhood excessive body weight (EBW) is associated with changes in serum NO level and whether features like age and gender are linked to NO levels in selected groups.. In the present study, the serum NO levels were compared in 43 children with EBW and 37 ageand gender-matched children with normal weight. Moreover, in both groups, body measurements and various clinical parameters, including the serum concentrations of arginine (Arg), a precursor of NO, were determined.. The mean serum NO level in EBW group (8.7 ±3.1 μmol/L) was significantly lower than in normal weight group (22.2 ±11.5 μmol/L). However, the serum Arg concentrations were higher in EBW children than in controls. Serum asymmetric dimethylarginine (ADMA) levels were higher in EBW group and inversely correlated with serum NO. The EBW female subgroup was characterized by slightly lower level of NO than the EBW male subgroup. There were no significant changes in serum NO level among different age subgroups in both groups.. Our results revealed that EBW in children is associated with significantly decreased level of serum NO. The decreased serum NO level in EBW children is not a result of depleted Arg in the blood. Asymmetric dimethylarginine may at least partially contribute to decreased NO levels in children with EBW. A decreased level of NO could be a potential early marker of the risk of cardiovascular disorders developing in children with EBW.

Topics: Adolescent; Arginine; Biomarkers; Body Weight; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Nitric Oxide; Obesity

This study was designed to investigate whether rosuvastatin could attenuate monocrotaline-induced pulmonary hypertension via regulation of Akt/eNOS signaling pathway and asymmetric dimethylarginine (ADMA) metabolism in rats. After a single-dose injection of monocrotaline (60 mg/kg), oral administration of rosuvastatin (5mg/kg) was started from day 1 to day 28 (preventive administration) or from day 15 to day 28 (therapeutic administration), or with vehicle as corresponding controls. 28 days after monocrotaline, significant pulmonary hypertension characterized by pulmonary arterial medial wall thickening, right ventricular hypertrophy and right heart failure was observed. Rosuvastatin (5mg/kg, for 14 days and 28 days) treatment significantly attenuated monocrotaline-induced pulmonary vascular remodeling, right ventricular hypertrophy and dysfunction, and normalized the down-regulated pulmonary Akt/p-Akt and eNOS/p-eNOS expressions, while increased DDAH2 expression accompanied by decreased serum level of ADMA. However expression of PRMT1 and GSK3β/p-GSK3β did not differ among all groups (all P>0.05). We concluded that rosuvastatin inhibits monocrotaline-induced pulmonary hypertension through normalization of Akt, eNOS and DDAH2 expressions, and decreasing the level of ADMA.

Topics: Amidohydrolases; Animals; Arginine; Biomarkers; Body Weight; Fluorobenzenes; Gene Expression Regulation, Enzymologic; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart; Hypertension, Pulmonary; Lung; Male; Monocrotaline; Nitric Oxide Synthase Type III; Organ Size; Protein-Arginine N-Methyltransferases; Proto-Oncogene Proteins c-akt; Pyrimidines; Rats; Rats, Sprague-Dawley; Rosuvastatin Calcium; Signal Transduction; Sulfonamides; Ventricular Dysfunction, Right

Maternal undernutrition can cause reduced nephron number and glomerular hypertrophy, consequently leading to adult kidney disease. We intended to elucidate whether NO deficiency evolves to kidney disease vulnerability in offspring from mothers with caloric restriction diets and whether maternal L-citrulline (L-Cit) supplementation can prevent this. Using a rat model with 50% caloric restriction, four groups of 3-month-old male offspring were sacrificed to determine their renal outcome: control, caloric restriction (CR), control treated with 0.25% L-citrulline solution during the whole period of pregnancy and lactation (Cit), and CR treated in the same way (CR+Cit group). The CR group had low nephron numbers, increased glomerular diameter, and an increased plasma creatinine level compared with the control group. Maternal L-Cit supplementation prevented these effects. The CR+Cit and Cit groups developed hypertension beginning at 4 and 8weeks of age, respectively. Plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels were increased, but L-arginine/ADMA ratios (AAR) were decreased in the CR group vs the control group. This was prevented by maternal L-Cit supplementation. Renal cortical neuronal NOS-alpha (nNOSalpha) protein abundance was significantly decreased in the Cit and CR+Cit groups. Collectively, reduced nephron number, reduced renal nNOSalpha expression, increased ADMA, and decreased AAR contribute to the developmental programming of adult kidney disease and hypertension. Although maternal L-Cit supplementation prevents caloric restriction-induced low nephron number and renal dysfunction, it also induces hypertension.

Topics: Analysis of Variance; Animals; Animals, Newborn; Arginine; Blood Pressure; Blotting, Western; Body Weight; Caloric Restriction; Citrulline; Female; Histocytochemistry; Kidney; Kidney Cortex; Kidney Glomerulus; Male; Maternal Exposure; Nephrons; Nitric Oxide; Pregnancy; Rats; Signal Transduction

In the context of the hypercatabolic response to stress, critically ill patients reveal hyperglycemia and elevated levels of asymmetrical-dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases. Both hyperglycemia and elevated ADMA levels predict increased morbidity and mortality. Tight glycemic control by intensive insulin therapy lowers circulating ADMA levels, and improves morbidity and mortality. Methylarginines are released from proteins during catabolism. ADMA is predominantly cleared by the enzyme dimethylarginine-dimethylaminohydrolase (DDAH) in different tissues, whereas its symmetrical isoform (SDMA) is cleared via the kidneys. Therefore, glycemic control or glycemia-independent actions of insulin on protein breakdown and/or on DDAH activity resulting in augmented ADMA levels may explain part of the clinical benefit of intensive insulin therapy. Therefore, we investigated in our animal model of prolonged critical illness the relative impact of maintaining normoglycemia and of glycemia-independent action of insulin over 7 d in a four-arm design on plasma and tissue levels of ADMA and SDMA, on proteolysis as revealed by surrogate parameters as changes of body weight, plasma urea to creatinine ratio, and plasma levels of SDMA, and on tissue DDAH activity. We found that ADMA levels remained normal in the two normoglycemic groups and increased in hyperglycemic groups. SDMA levels in the investigated tissues remained largely unaffected. The urea to creatinine ratio indicated reduced proteolysis in all but normoglycemic/normal insulin animals. DDAH activity deteriorated in hyperglycemic compared with normoglycemic groups. Insulin did not affect this finding independent of glycemic control action. Conclusively, maintenance of normoglycemia and not glycemia-independent actions of insulin maintained physiological ADMA plasma and tissue levels by preserving physiological DDAH activity.

Topics: Amidohydrolases; Animals; Arginine; Blood Glucose; Body Weight; Creatinine; Critical Illness; Disease Models, Animal; Humans; Insulin; Rabbits

Asymmetric dimethylarginine (ADMA) is a marker of various cardiovascular diseases in man. The aim of the present study was to test if Cavalier King Charles Spaniels (CKCS) with varying degrees of mitral regurgitation (MR) had increased plasma concentration of ADMA and furthermore, characterize the plasma level of ADMA and symmetric dimethylarginine (SDMA) in normal dogs. Seventy-six dogs were included (44 CKCS and 32 dogs of other breeds). The CKCS had various degrees of MR, whereas the remaining dogs had either no or minimal MR. Apart from cardiac murmurs, no dogs showed signs of cardiac or systematic disease. The degree of MR had no significant influence on ADMA (P = 0.33). Body weight was directly associated with ADMA (P = 0.0004) and creatinine was directly associated with SDMA (P<0.0001). Furthermore, the plasma concentration of ADMA was three to four times higher than found in healthy humans.

Topics: Age Factors; Animals; Arginine; Body Weight; Creatinine; Dog Diseases; Dogs; Female; Linear Models; Male; Mitral Valve Insufficiency; Mitral Valve Prolapse; Sex Factors

Infants born term have substantially elevated plasma concentrations of the endogenous nitric oxide synthase antagonist asymmetrical dimethylarginine (ADMA) that normalize with growth. The plasma levels of ADMA in preterm newborns are unknown.. Plasma concentrations of ADMA, symmetrical dimethylarginine (SDMA) and L-arginine were analyzed from venous umbilical cord blood samples of 19 preterm and 21 term infants by high performance liquid chromatography.. Male preterm newborns (n=11) had higher ADMA (median [95% confidence interval (CI)]: 1.90 [1.73-2.10] micromol/l) than females born preterm (n=8; 1.57 [1.24-1.69] micromol/l; p<0.005). In term born males (n=10) and females (n=11) ADMA was significantly lower than in preterm male infants (all p<0.005), and without sex differences. SDMA and L-arginine concentrations were comparable between all groups. ADMA correlated inversely with body weight in male preterm newborns (r=-0.67; p<0.03).. Male neonates delivered preterm have significantly higher umbilical cord venous plasma concentrations of ADMA compared to female neonates and infants born term. The sex difference and the time course of elevated ADMA may play a role in development and warrant further investigation.

Topics: Arginine; Blood Circulation; Body Weight; Female; Fetal Blood; Humans; Infant, Newborn; Male; Nitric Oxide Synthase; Pilot Projects; Premature Birth; Sex Characteristics; Time Factors