Nitric Oxide Research

Luiking YC, Engelen MPKJ, Deutz NEP. Regulation of nitric oxide production in health and disease. Curr Opin Clin Nutr Metab Care 2010; 13(1): 97-104.

  • 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 NO production.
  • Citrulline supplementation may therefore be a novel therapeutic approach in conditions of arginine deficiency. x Abnormalities in vascular NO production and transport result in endothelial dysfunction with various cardiovascular pathologies like hypertension, atherosclerosis, and angiogenesis-associated disorders.
  • Interestingly, NOS3 can generate superoxide when the concentrations of either L-arginine or BH4 are low. This “uncoupling” of NOS3 occurs in several pathologies, like diabetes, hypercholesterolemia, and hypertension.
  • NO production was also suggested as a major inherited factor of insulin sensitivity, with diet-induced oxidative scavenging of NO as a first hit towards insulin resistance.
  • Arginase has been proposed as an attractive therapy in modifying the arterial response to injury and may offer therapeutic interventions in the treatment of vascular disease.

Ali EMM, Hamdy SM, Mohamed TM. Nitric oxide synthase and oxidative stress: regulation of nitric oxide synthase.

  • Thus, arginase has recently emerged as a critical regulator of NO synthesis that may contribute to the development of numerous pathologies, including vascular disease.