Agmatine Produced by Arginine Decarboxylase Activity Causes NO Dependent Rat Mesenteric Artery Relaxation

Aim To determine if agmatine produced from arginine causes endothelium‐dependent arterial relaxation. Background We have shown that arginine relaxes vessels via α‐2 adrenergic receptor (PNAS, 104, 9982, 2007). However, high arginine concentrations were required to see any measurable effect, which raises the possibility that the actions of arginine may be mediated by agmatine via arginine decarboxylase (ADC). Therefore, we have investigated the effects of ADC inhibition on the arterial relaxation. Methods Isolated 2 nd order mesenteric arterioles from rats were cannulated at both ends and pre‐constricted with norepinephrine (2 μM) in a vessel chamber that was perfused intraluminally with modified Krebs buffer at 37°C. Cannulated vessels were pressurized at 50 mmHg and allowed to equilibrate for 60 min before initiating the experiment. Results L‐arginine dose‐dependently relaxed the vessel (EC 50 , 5.87±0.75 mM; n=7). These relaxations were inhibited by more than 50% with DL‐α‐Difluoromethylarginine (DFMA, 1mM), a potent ADC inhibitor (EC 50 , 13.83±1.68 mM; n=3). The relaxation to agmatine (EC 50 , 129.24±13.9 μM; n=18) was inhibited in presence of G‐protein blocker pertussis toxin (PTX, 50 nM) (EC 50 , 481.25 μM; n=1). Conclusion Arginine causes rat mesenteric artery relaxation via agmatine produced by ADC activity and GPCR mediate the relaxation by agmatine. This work was supported by NIH grant.