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Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on acute lipoprotein induced endothelial dysfunction in rabbit aortic rings
Author(s) -
Fontana L,
McNeill K L,
Ritter J M,
Chowienczyk P J
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702331
Subject(s) - chemistry , superoxide dismutase , acetylcholine , endocrinology , endothelium , medicine , superoxide , arginine , vitamin e , nitric oxide , lipoprotein , biochemistry , antioxidant , cholesterol , amino acid , enzyme
Low density lipoprotein (LDL) inhibits endothelium‐dependent relaxation. The mechanism is uncertain, but increased production of superoxide anion O 2 − 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 O 2 − 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 μ M ) reduced inhibitory effects of LDL from 124±27 to 56±17% ( n =6, P <0.05). Vitamin C (1 m M ) 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 m M ) did not differ significantly from those of D ‐arginine (10 m M ). 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 O 2 − generation.British Journal of Pharmacology (1999) 126 , 730–734; doi: 10.1038/sj.bjp.0702331