Low molecular mass dinitrosyl nonheme-iron complexes up-regulate noradrenaline release in the rat tail artery
1 Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, CNRS, UMR 7034, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, 67401 Illkirch, France
2 University Hospital Hamburg-Eppendorf, Division of Cardiology, Hamburg 20246, Germany
BMC Pharmacology 2002, 2:3 doi:10.1186/1471-2210-2-3Published: 8 February 2002
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.
A model complex, dinitrosyl-iron-thiosulfate (at 1–10 μM) 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 μM) 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 μM) had no effect on [3H]noradrenaline release, though they potently decreased electrically-induced vasoconstriction. The "false complex", iron(II)-thiosulfate showed no activity.
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.