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Early studies of mammalian nitrogen oxide biosynthesis began with the rationale that endogenously formed nitrogen oxides could generate N-nitrosamines and, thus, initiate carcinogenesis (7). Since then, our understanding of the biologic consequences of nitrogen oxide biosynthesis has expanded considerably. Following its initial discovery in macrophages (2), nitrogen oxide biosynthesis has been demonstrated in endothelial cells (3,4), neutrophils (5,6), brain cells (7-9), Kupffer's cells (10), hepatocytes (11), an adenocarcinoma cell line (72), and the adrenal gland (73). Investigators using N in studies of macrophages and endothelial cells (14,15) confirmed that nitrogen oxides are formed from one of the two equivalent guanidino nitrogens of L-arginine. The primary products of this enzymatic oxidation are nitric oxide and L-citrulline (3,4,11,16-18). Nitric oxide is bioactive but decomposes rapidly in aerated solutions to form mixtures of nitrite and nitrate.

Does Endothelium-Derived Nitric Oxide Have a Rolein Cytokine-Induced Hypotension?