Vascular endothelial cells synthesize nitric oxide from L-arginine

Abstract

Nitric oxide (NO) released by vascular endothelial cells accounts for the relaxation of strips of vascular tissue¹ and for the inhibition of platelet aggregation² and platelet adhesion³ attributed to endothelium-derived relaxing factor⁴. We now demonstrate that NO can be synthesized from L-arginine by porcine aortic endothelial cells in culture. Nitric oxide was detected by bioassay⁵, chemiluminescence¹ or by mass spectrometry. Release of NO from the endothelial cells induced by bradykinin and the calcium ionophore A23187 was reversibly enhanced by infusions of L-arginine and L-citrulline, but not D-arginine or other close structural analogues. Mass spectrometry studies using ¹⁵N-labelled L-arginine indicated that this enhancement was due to the formation of NO from the terminal guanidino nitrogen atom(s) of L-arginine. The strict substrate specificity of this reaction suggests that L-arginine is the precursor for NO synthesis in vascular endothelial cells.