N G ,N G -Dimethyl-l-arginine, a dominant precursor of endogenous dimethylamine in rats

Abstract

The metabolic significance ofN (G) ,N (G) -dimethyl-L-arginine (DMA) as a precursor of endogenous dimethylamine (DMN) in rats was examined in connection with the wide distribution and active operation of dimethylargininase (EC3.5.3.18) in rat tissues (Kimoto et al., 1993). When [methyl-(14)C]DMA was administered intraperitoneally to rats, the radioactive DMN was detected in various tissues as a major radioactive metabolite one hour after injection, and about 65% of the radioactivity administered was recovered in the first 12-h urine as DMN. In the case of the [(14)C] DMN-injected rats, almost all the radioactivity was excreted in the 12-h urine as DMN, except for a negligible amount of radioactivity found in urea. The time-dependent decrease in the specific radioactivity of DMA and DMN in urine showed that dimethylargininase was significantly involved in thein vivo formation of DMN by the hydrolytic cleavage of DMA released from methylated proteins and that DMA is a dominant precursor of endogenous DMN in rats.

Nitric oxide synthase inhibitors and hypertension in children and adolescents

“…L-NMMA, ADMA and SDMA are synthesized by a variety of cells [47], including human endothelial cells [48]. We have demonstrated in this study that ADMA and SDMA levels are raised in the plasma of children with hypertension.…”

“…Experimentally, a ninefold rise in plasma ADMA to 9.8 ± 1.7 mol/l (with infusion of ADMA) in guinea pigs has been shown to be associated with a 15% rise in systolic blood pressure [17]. Because ADMA and SDMA are agents produced by endothelial cells, the local or intracellular concentrations of these substances are likely to be much higher (for instance 35 mol/l in the kidney [47]) than those detected in plasma and hence are likely to produce a more significant response in vivo than those demonstrable in vitro. Nonetheless, in this study we have demonstrated that concentrations of arginine analogues found in childhood hypertensives, in particular of ADMA, are capable of initiating a physiological response in mouse aortic rings.…”

Urinary Dimethylamine (DMA) and Its Precursor Asymmetric Dimethylarginine (ADMA) in Clinical Medicine, in the Context of Nitric Oxide (NO) and Beyond

“…A likely precursor of DMA is trimethylamine N-oxide (TMAO). In the rat, administered radiolabeled TMAO ( 14 C-TMAO) was found to be excreted in part unchanged and in part as 14 C-DMA [18]. In the same study, TMAO was found to be converted to DMA when incubated with the colon and rectum, indicating bacterial…”

“…SDMA is not metabolized by DDAH. This enzyme was first discovered in rats, which were found to metabolize ADMA to DMA [ 13 , 14 ]. In adults, about 90% of daily produced ADMA are estimated to be hydrolyzed to DMA, with the remaining 10% being excreted unchanged in the urine ( Figure 2 ).…”