Divergent effects of vitamin C on relaxations of rabbit aortic rings to acetylcholine and NO-donors

1Vitamin C may influence NO-dependent relaxation independently of effects on oxidant stress. 2 We investigated effects of vitamin C (0.1 - 10 mmol 1(-1)) on relaxation of pre-constricted rabbit aortic rings to acetylcholine (ACh), authentic NO and the NO-donors glyceryl trinitrate (GTN), nitroprusside (NP) and S-nitroso-N-acetyl-penicillamine (SNAP). DETCA (2 - 6 mmol 1(-1)), a cell permeable inhibitor of endogenous Cu-Zn superoxide dismutase (SOD) was used to increase intracellular superoxide anion (O-2(-)). 3 Vitamin C reduced the response to ACh (71+/-7% inhibition of maximum relaxation at 10 mmol 1(-1)) and inhibited relaxation to authentic NO. Vitamin C inhibited relaxation to GTN but potentiated relaxations to NP and SNAP, causing a parallel shift to a lower concentration range of the log dose-response curve by approximately one log unit at the highest dose. 4 Vitamin C increased the concentration of NO in bath solution (plus EDTA, 1.0 mmol 1(-1)) following the addition of SNAP from 53+/-14 to 771+/-101 nmol 1(-1) over the range 0.1-3.0 mmol 1(-1). 5 DETCA inhibited relaxation to ACh (71+/-9% inhibition of maximum relaxation). This inhibition was abolished by a cell permeable SOD mimetic, but not by vitamin C. DETCA inhibited relaxation to SNAP but not that to NP nor to GTN. 6 Vitamin C inhibits endothelium-dependent relaxations of rabbit aortic rings to ACh and authentic NO and does not reverse impaired relaxation resulting from increased intracellular oxidant stress. Vitamin C potentiates relaxation to the NO-donors NP and SNAP by a mechanism that could involve release of NO from nitrosothiols.