Regulation of nitric oxide production in health and disease.
OBJECTIVE
The purpose of this review is to highlight recent publications examining nitric oxide production in health and disease and its association with clinical nutrition and alterations in metabolism.


RESULTS
The role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial nitric oxide production is often impaired due to a reduction in nitric oxide synthase 3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was, therefore, proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de-novo arginine production from citrulline reduces nitric oxide production. Citrulline supplementation may, therefore, be a novel therapeutic approach in conditions of arginine deficiency.


CONCLUSIONS
Both lack and excess of nitric oxide production in diseases can have various important implications in which dietary factors can play a modulating role. Future research is needed to expand our understanding of the regulation and adequate measurement of nitric oxide production at the organ level and by the different nitric oxide synthase isoforms, also in relation to clinical nutrition.
Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Yvette C
YC
Luiking
Mariëlle P K J
MP
Engelen
Nicolaas E P
NE
Deutz
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors; D001120:Arginine / Q000378:metabolism* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000097:blood / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000178:diet therapy / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D018805:Sepsis / Q000378:metabolism
D004041:Dietary Fats; D001708:Biopterins; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D001119:Arginase; C003402:sapropterin; D001205:Ascorbic Acid