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

摘要

class="enumerated" style="list-style-type:decimal">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, P<0.001) but not to the endothelium-independent agonist nitroprusside.MnTMPyP (10 μM) reduced inhibitory effects of LDL from 124±27 to 56±17% (n=6, P<0.05).Vitamin C (1  mM) reduced inhibitory effects of LDL from 59±8 to 22±5% (n=6, P<0.05).Inhibitory effects of LDL were similar in the absence or presence of arginine (84±12 vs 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.