Pioglitazone Lowers Systemic Asymmetric Dimethylarginine by Inducing Dimethylarginine Dimethylaminohydrolase in Rats

@article{Wakino2005PioglitazoneLS,
  title={Pioglitazone Lowers Systemic Asymmetric Dimethylarginine by Inducing Dimethylarginine Dimethylaminohydrolase in Rats},
  author={Shu Wakino and Koichi Hayashi and Satoru Tatematsu and Kazuhiro Hasegawa and Ichiro Takamatsu and Takeshi Kanda and Koichiro Homma and Kyoko Yoshioka and Naoki Sugano and Takao Saruta},
  journal={Hypertension Research},
  year={2005},
  volume={28},
  pages={255-262}
}
Peroxisome proliferator activated receptor-γ (PPARγ) ligands increase nitric oxide (NO) production and reduce systemic blood pressure. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which has two isoforms, DDAH-I and -II. In order to elucidate the mechanism whereby PPARγ ligands affect NO metabolism, their effects on the DDAH-ADMA pathway were investigated. Six-week-old male Wister… 
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Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems.

Evidence of rapidly evolving evidence of isoform-specific distribution and regulation of DDAH expression in the kidney and blood vessels provides potential mechanisms for nephron site-specific regulation of NO production.

Dimethylarginine dimethylaminohydrolase regulation: a novel therapeutic target in cardiovascular disease

The current role of ADMA and D DAH in vascular health and disease, the techniques used to assess DDAH activity and expression, and the results of recent studies on pharmacological and biological agents modulating DDAh activity andexpression are discussed.

Asymmetric Dimethylarginine, an Endogenous NOS Inhibitor, Is Actively Metabolized in Rat Erythrocytes

This is the first report that the ADMA-metabolizing system, including the arginine methylation of proteins and the breakdown of free ADMA, occurs in circulating blood cell-populations, and that catalase in ECs might be a potential protein targeted by PRMT1.

Asymmetric Dimethylarginine Synthesis and Degradation Under Physiological and Pathological Conditions

In various pathological states such as hypercholesterolemia, hyperglycemia,hyperhomocysteinemia, hypertension, coronary artery disease, heart failure, and stroke, plasma levels of ADMA may increase twoor even tenfold, contributing to inhibition of NO synthesis and endothelial dysfunction.

cAMP Phosphodiesterase Inhibitors Increases Nitric Oxide Production by Modulating Dimethylarginine Dimethylaminohydrolases

Combined inhibition of PDE3 and 4 regresses development of pulmonary hypertension and promotes endothelial regeneration by modulating the ADMA-DDAH axis.

The clinical significance of asymmetric dimethylarginine.

Interestingly, next to its association with cardiovascular disease, ADMA also seems to play a role in other clinical conditions, such as critical illness, hepatic failure, and preeclampsia, and the field of research must be enlarged to elucidate the clinical significance of ADMA in these conditions.

Asymmetric dimethylarginine : assay methodology and serum levels in non-pregnant and pregnant women

It was found that the ADMA concentration varied during menstrual cycle and was dependent on hormonal status of women without oral contraceptive (OC) use, and ADMA, SDMA and L-arginine concentrations were elevated in normal pregnancy in comparison with the levels in non-pregnant females.

Pioglitazone decreases asymmetric dimethylarginine levels in patients with impaired glucose tolerance or type 2 diabetes.

It is demonstrated that pioglitazone decreased serum ADMA levels in a glucose-lowering independent manner and may contribute to the reduction of serum levels of ADMA in IGT or T2DM subjects, thus playing a protective role against cardiovascular disease.

cAMP Phosphodiesterase Inhibitors Increases Nitric Oxide Production by Modulating Dimethylarginine Dimethylaminohydrolases

This work investigated whether combined phosphodiesterase (PDE) 3 and 4 inhibition ameliorates endothelial function by regulating the ADMA-DDAH axis by investigating the effects of the PDE3/4 inhibitor tolafentrine in vitro on endothelial cell survival, proliferation, and apoptosis.

Asymmetric Dimethylarginine (ADMA) and Endothelial Dysfunction: Implications for Atherogenesis

Several basic science and clinical research studies suggest that the increase in asymmetric dimethylarginine occurs in the context of chronic renal insufficiency, dyslipidemia, high blood pressure, diabetes mellitus, and hyperhomocysteinemy, as well as with other conditions.
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