Evaluation of vascular actions of the nitric oxide-trapping agent, N-methyl-D-glucamine dithiocarbamate-Fe2+, on basal and agonist-stimulated nitric oxide activity.
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.
Pieper
G M
GM
Department of Transplant Surgery, Medical College of Wisconsin, Froedtert Memorial Hospital, Milwaukee 53226, USA.
Lai
C S
CS
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013113:Spin Labels; D013859:Thiocarbamates / Q000494:pharmacology*
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D013113:Spin Labels; D013859:Thiocarbamates; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D013012:Sorbitol; C041262:N-methyl-D-glucamine dithiocarbamate; D001120:Arginine; D007501:Iron; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin