NG,NG-dimethyl-L-Arginine (hydrochloride)

NG,NG-dimethyl-L-Arginine is an endogenous nitric oxide synthase inhibitor.

Nitric oxide (NO) that is synthesised from L-arginine contributes to the regulation of blood pressure and to host defence.

In vitro: NG,NG-dimethyl-L-Arginine (ADMA) was found to be able to inhibit macrophage and vascular NO synthase. When added to a cytosolic preparation of macrophage NO synthase, ADMA could cause dose-dependent inhibition of NO formation. In the presence of added arginine, ADMA could inhibited NO synthesis and the inhibitory effects of ADMA were prevented by addition of L-arginine so that the rate of NO synthesis did not significantly differ from control values [1].

In vivo: Animal study showed that the injection of 1-30 mg/kg ADMA into 3 anaesthetised guineapigs could cause dose-dependent increases in mean arterial blood pressure. Moreover, during continuous infusion of ADMA, which caused plasma ADMA concentrations to rise approximately 9-fold, the systolic blood pressure was raised by nearly 15 % [1].

Clinical trial: Local infusion of ADMA into the brachial artery of healthy volunteers caused a dose-dependent fall in forearm blood-flow. Infusion of ADMA for 5 min resulted in a fall in forearm blood-flow in 5 subjects, and the effects of this ADMA dose were significantly attenuated by infusion of L-arginine [1].

Reference:
[1] Vallance, P. ,Leone, A.,Calver, A., et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339, 572-575 (1992).