Arginine metabolism in vascular biology and disease

Arginine metabolism plays a major role in cardiovascular physiology and pathophysiology, largely via nitric oxide (NO)-dependent processes. It is becoming increasingly apparent, however, that arginine metabolic enzymes other than the NO synthases can also play important roles via both NO-dependent and -independent processes. There are three sources of arginine in vivo and at least five mammalian enzymes or enzyme families that utilize arginine as substrate. Changes in arginine availability or in production of the different end products of the various arginine metabolic pathways can have distinct and profound physiologic consequences. However, our knowledge regarding the complex interplay between these pathways at the level of the whole body, specific tissues, and even individual cells, is incomplete. This review will highlight recent findings in this area that may suggest additional avenues of investigation that will allow a fuller understanding of cardiovascular physiology in health and disease.