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

Br J Pharmacol. 1999 Feb;126(3):730-4. doi: 10.1038/sj.bjp.0702331.

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 microg protein ml(-1) for 20 min) markedly inhibited relaxation of aortic rings (in Krebs' solution at 37 degrees 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 microM) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / physiopathology
  • Arginine / pharmacology
  • Ascorbic Acid / pharmacology*
  • Cell Membrane Permeability
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Free Radical Scavengers / pharmacology*
  • Humans
  • In Vitro Techniques
  • Lipoproteins / pharmacology*
  • Lipoproteins, LDL / pharmacology
  • Male
  • Metalloporphyrins / pharmacology*
  • Middle Aged
  • Muscle Relaxation / drug effects
  • Nitroprusside / pharmacology
  • Rabbits
  • Superoxide Dismutase / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • Free Radical Scavengers
  • Lipoproteins
  • Lipoproteins, LDL
  • Metalloporphyrins
  • Vasodilator Agents
  • Nitroprusside
  • tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex
  • Arginine
  • Superoxide Dismutase
  • Acetylcholine
  • Ascorbic Acid