Low molecular mass dinitrosyl nonheme-iron complexes up-regulate noradrenaline release in the rat tail artery.
BACKGROUND
Dinitrosyl nonheme-iron complexes can appear in cells and tissues overproducing nitric oxide. It is believed that due to their chemical nature these species may be implicated in certain pathophysiological events. We studied the possible role of low molecular mass dinitrosyl iron complexes in the control of noradrenaline release in electrically stimulated rat tail artery.


RESULTS
A model complex, dinitrosyl-iron-thiosulfate (at 1-10 microM) produced a concentration-dependent enhancement of electrical field stimulated [3H]noradrenaline release (up to 2 fold). At the same time, dinitrosyl-iron-thiosulfate inhibited neurogenic vasoconstriction, consistent with its nitric oxide donor properties. A specific inhibitor of cyclic GMP dependent protein kinase, Rp-8pCPT-cGMPS, partially inhibited the effect of dinitrosyl-iron-thiosulfate on neurogenic vasoconstriction, but not on [3H]noradrenaline release. Another model complex, dinitrosyl-iron-cysteine (at 3 microM) elicited similar responses as dinitrosyl-iron-thiosulfate. Conventional NO and NO+ donors such as sodium nitroprusside, S-nitroso-L-cysteine or S-nitroso-glutathione (at 10 microM) had no effect on [3H]noradrenaline release, though they potently decreased electrically-induced vasoconstriction. The "false complex", iron(II)-thiosulfate showed no activity.


CONCLUSIONS
Low molecular mass iron dinitrosyl complexes can up-regulate the stimulation-evoked release of vascular [3H]noradrenaline, apparently independently of their NO donor properties. This finding may have important implications in inflammatory tissues.
Kleschyov
Andrei L
AL
Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, CNRS, UMR 7034, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 67401 Illkirch, France. kleschyo@uke.uni-hamburg.de
Hubert
Gilles
G
Munzel
Thomas
T
Stoclet
Jean-Claude
JC
Bucher
Bernard
B
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D009589:Nitrogen Oxides / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000166:cytology; D014316:Tritium
D009589:Nitrogen Oxides; D014316:Tritium; C073661:dinitrosyl iron complex; D007501:Iron; D017869:Cyclic GMP-Dependent Protein Kinases; D009638:Norepinephrine