Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on acute lipoprotein induced endothelial dysfunction in rabbit aortic rings

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Abstract
Low density lipoprotein (LDL) inhibits endothelium‐dependent relaxation. The mechanism is uncertain, but increased production of superoxide anion O2− with inactivation of endothelium‐derived NO and formation of toxic free radical species have been implicated. We investigated effects of the cell permeable superoxide dismutase mimetic manganese (III) tetrakis (1‐methyl‐4‐pyridyl) porphyrin (MnTMPyP), the free radical scavenger vitamin C and arginine (which may reduce O2− formation) on acute LDL‐induced endothelial dysfunction in rabbit aortic rings, using LDL prepared by ultracentrifugation of plasma from healthy men and aortic rings from New Zealand white rabbits. LDL (150 μg protein ml−1 for 20 min) markedly inhibited relaxation of aortic rings (in Krebs' solution at 37°C and pre‐constricted to 80% maximum tension with noradrenaline) to acetylcholine 82±10% (mean percentage difference between sum of relaxations after each concentration of acetylcholine in the presence and absence of LDL, ±s.e.mean, n=26, Pn=6, Pn=6, Pvs 79±16%, n=14, P=0.55). Effects of L‐arginine (10 mM) did not differ significantly from those of D‐arginine (10 mM). Acute (20 min) exposure of aortic rings to LDL impairs endothelium‐dependent relaxation which can be partially restored by MnTMPyP and vitamin C. This is consistent with LDL causing increased O2− generation. British Journal of Pharmacology (1999) 126, 730–734; doi:10.1038/sj.bjp.0702331

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