Agmatine‐mediated rat mesenteric artery relaxation via NO synthesis

Abstract

AimTo determine membrane receptor‐dependent or independent mechanisms of agmatine (decarboxylated arginine) relaxation of rat mesenteric arteries.BackgroundIn spite of excess levels of intracellular L‐arginine, exogenous L‐arginine still activates cellular synthesis of nitric oxide (NO) in a phenomenon called “arginine paradox”. Our previously published data (PNAS, 104, 9982, 2007) show that L‐arginine or agmatine may be initiating the NO synthesis via receptor binding and release of intracellular Ca+2 in endothelial cells. Here we have tested the same mechanism in isolated rat mesenteric arteries.MethodsThe individual 2nd order mesenteric arteriolar segments from rats (250–300 g male, Sprague‐Dawley) were cannulated at both ends in a vessel chamber that was continuously perfused intraluminally and pre‐constricted with norepinephrine (2 μM) in modified Krebs buffer at 37°C. For internal diameter measurements, the vessel chamber was mounted on the stage of a microscope fitted with a video camera leading to video caliper. Mounted vessels were allowed to stabilize for 60 min before initiating experiment.ResultsThe data show that agmatine completely relaxed the vessel with an EC50 of 58.75 ± 12.1 μM (n=4) and this relaxation could be significantly inhibited with nitric oxide synthase inhibitor, L‐NAME (0.5 mM) with EC50 of 315 μM (n=1).ConclusionAgmatine dose‐dependently relaxed the rat mesenteric artery and NO mediated the relaxation process.This work was supported in part by NIH grant SC1HL095101