Evaluation of vascular actions of the nitric oxide-trapping agent, N-methyl-D-glucamine dithiocarbamate-Fe2+, on basal and agonist-stimulated nitric oxide activity

Biochem Biophys Res Commun. 1996 Feb 15;219(2):584-90. doi: 10.1006/bbrc.1996.0277.

Abstract

The NO scavenger, N-methyl-D-glucamine dithiocarbamate-Fe2+ (MGD-Fe), was used to characterize spontaneous and agonist-stimulated NO activity arising from rat aortic endothelium. Scavenging of NO in solution by MGD-Fe without tissue was confirmed by electron paramagnetic resonance spectroscopy. The addition of MGD-Fe to aortic ring segments suspended in vitro under resting tension did not cause any direct contraction, but when added to rings contracted with phenylephrine elicited a rapid additional increment in tension which was not altered by indomethacin. This increase in tension was absent in rings pretreated with L-nitroarginine or in rings without endothelium; however, the developed tension in both instances was similar in magnitude to that seen after MGD-Fe suggesting complete scavenging of basal NO production. Acetylcholine produced relaxation (maximum relaxation = 100 +/- 1%) which was completely eliminated in the presence of L-nitroarginine or upon removal of the endothelium. Relaxation to acetylcholine was reduced to 56 +/- 8% in the presence of MGD-Fe (3.0/0.6 mM ratio). Higher concentrations of MGD-Fe caused further decreases in the maximum relaxation to acetylcholine; however, a residual component (approx. 30%) of relaxation persisted. This effect was mimicked by using another NO trapping agent, carboxy-PTIO. These data suggest that MGD-Fe scavenges agonist-stimulated NO, but also reveals a NO synthase-dependent component which is unavailable to interact with MGD-Fe.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Chelating Agents / pharmacology*
  • Electron Spin Resonance Spectroscopy
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Iron / pharmacology
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Nitroarginine
  • Norepinephrine / pharmacology
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sorbitol / analogs & derivatives*
  • Sorbitol / pharmacology
  • Spin Labels
  • Thiocarbamates / pharmacology*

Substances

  • Chelating Agents
  • Enzyme Inhibitors
  • Spin Labels
  • Thiocarbamates
  • Phenylephrine
  • Nitroarginine
  • Nitric Oxide
  • Sorbitol
  • N-methyl-D-glucamine dithiocarbamate
  • Arginine
  • Iron
  • Nitric Oxide Synthase
  • Acetylcholine
  • Norepinephrine
  • Indomethacin