Asymmetric Dimethylarginine의 다형핵 백혈구에 대한 효과

Abstract

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, has been suggested to be a contributory factor in vascular disease of atheroclerosis. The present study was undertaken to elucidate the effects of ADMA on the vasorelaxation of isolated thoracic aorta, PMNs adherence to superior mesenteric artery, the generation of superoxide and hydrogen peroxide in PMNs, and the intracellular calcium mobilization in PMNs. The endothelium dependent vasorelaxation of isolated thoracic aorta was inhibited by ADMA in a dose-dependent manner, but the endothelium independent vasorelaxation was not inhibited by ADMA. The PMNs adherence to superior mesenteric artery was increased by ADMA. Superoxide anion and hydrogen peroxide production in 1 μM formylmethionylleucylpheylalanine (fMLP)-activated PMNs was increased by ADMA in a dose-dependent fashion. The fMLP-induced elevation of intracelluar calcium in PMNs was inhibited by ADMA. L-arginine reversed the effects of ADMA on the vasorelaxation of isolated thoracic aorta, PMNs adherence to superior mesenteric artery, the superoxide and hydrogen peroxide generation, and the elevation of intracellular calcium in PMNs. The results suggest that ADMA may be harmful to vascular endothelium by stimulating inflammatory cells, but L-arginine may protect vascular endothelium from the ADMA-induced damage.