of an endogenous inhibitor of nitric oxide synthesis in chronic ..

AB - We tested the hypothesis that the endogenous nitric oxide synthetase (NOS) inhibitor, asymmetric dimethylarginine (ADMA), regulates cardiovascular function by central mechanisms. In in vivo studies, rats received intracerebroventricular (i.c.v.) injection of isotonic saline, ADMA (1 mg), l-arginine (3 mg), and N(ω)-nitro-l-arginine methylester (l-NAME, 1 mg). Baroreflex function was then assessed by intravenous (i.v.) injection of phenylephrine. Central application of exogenous NOS inhibitor, l-NAME, increased mean arterial blood pressure and decreased heart rule. However, application of the endogenous NOS inhibitor, ADMA, decreased mean arterial blood pressure and heart rate simultaneously (-39 ± 6 mm Hg and -50 ± 8 beats/min, respectively). Both l-NAME (i.c.v.) and ADMA (i.c.v.) significantly inhibited the baroreflex function, indicating a regulatory role of central nitric oxide in controlling baroreflex function. In contrast to the central effect, intravenous injection of ADMA caused dose-dependent increases in mean arterial blood pressure that could be blocked by l-NAME pretreatment. In vitro studies using aortic rings demonstrated that ADMA (10-4 M) significantly increased the concentration of acetylcholine for the threshold response (EC15) and half-maximal response (EC50). This indicates that ADMA inhibits the constitutive isoform of NOS in the endothelium. ADMA may have functional importance in regulating cardiovascular function by mechanisms in addition to the inhibition of nitric oxide synthesis.

An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes ☆

S.PY - 1996/12/1Y1 - 1996/12/1N2 - We tested the hypothesis that the endogenous nitric oxide synthase (NOS) inhibitor, asymmetrical dimethylarginine (ADMA) regulates cardiovascular function via central mechanisms.


Accumulation of an endogenous inhibitor of nitric oxide synthesis ..

is an endogenously synthesized nitric oxide (NO) synthase inhibitor ..

N2 - We tested the hypothesis that the endogenous nitric oxide synthetase (NOS) inhibitor, asymmetric dimethylarginine (ADMA), regulates cardiovascular function by central mechanisms. In in vivo studies, rats received intracerebroventricular (i.c.v.) injection of isotonic saline, ADMA (1 mg), l-arginine (3 mg), and N(ω)-nitro-l-arginine methylester (l-NAME, 1 mg). Baroreflex function was then assessed by intravenous (i.v.) injection of phenylephrine. Central application of exogenous NOS inhibitor, l-NAME, increased mean arterial blood pressure and decreased heart rule. However, application of the endogenous NOS inhibitor, ADMA, decreased mean arterial blood pressure and heart rate simultaneously (-39 ± 6 mm Hg and -50 ± 8 beats/min, respectively). Both l-NAME (i.c.v.) and ADMA (i.c.v.) significantly inhibited the baroreflex function, indicating a regulatory role of central nitric oxide in controlling baroreflex function. In contrast to the central effect, intravenous injection of ADMA caused dose-dependent increases in mean arterial blood pressure that could be blocked by l-NAME pretreatment. In vitro studies using aortic rings demonstrated that ADMA (10-4 M) significantly increased the concentration of acetylcholine for the threshold response (EC15) and half-maximal response (EC50). This indicates that ADMA inhibits the constitutive isoform of NOS in the endothelium. ADMA may have functional importance in regulating cardiovascular function by mechanisms in addition to the inhibition of nitric oxide synthesis.


16-5-2012 · Endogenous nitric oxide synthase ..

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all isoforms of nitric oxide synthase, the enzyme that synthesizes nitric oxide from arginine. Elevated plasma concentrations of ADMA are associated with hypertension and other risk factors for cardiovascular disease. Symmetric dimethylarginine (SDMA), a stereoisomer of ADMA that does not inhibit nitric oxide synthase, is also present in plasma in concentrations that are almost equal to ADMA concentrations. Any analytical method used for the determination of ADMA should therefore be able to discriminate between ADMA and SDMA. In this chapter a high-performance liquid chromatography (HPLC) method for the simultaneous analysis of arginine, ADMA, and SDMA is described. Solid-phase extraction is used to isolate all basic amino acids. Subsequently, amino acids are converted into relatively stable adducts by derivatization with o-phthalaldehyde reagent containing mercaptopropionic acid. Derivatives are then separated by reversed-phase HPLC using isocratic elution and fluorescence detection. The method requires only 0.05-0.2 mL of sample, allowing the analysis of plasma from small laboratory animals. Because of its high precision, this method is particularly suited to detect small concentration differences between samples, e.g., in the assessment of ADMA metabolism at the organ level by measurement of arterio-venous concentration differences.