Potency and kinetics of nitric oxide-mediated vascular smooth muscle relaxation determined with flash photolysis of ruthenium nitrosyl chlorides.
Flash photolysis of thermally stable, photolabile 'caged' precursors permits rapid and precise changes of ligand concentration at their site of action. This approach was used to determine the concentration-dependence and time course of NO-mediated relaxation of aortic smooth muscle, by use of two photolabile NO donors, trichloronitrosylruthenium (Ru(NO)Cl3) and dipotassium pentachloronitrosylruthenate (K2Ru(NO)Cl5). At concentrations up to 500 microM, both compounds were non-toxic before photolysis, and produced non-toxic by-products on photolysis. Photolytic release of NO produced relaxations of intact and endothelium-denuded aortic rings precontracted with noradrenaline (0.1-0.5 microM), with an EC50 for NO-mediated relaxations of 10.5 nM and 13 nM, respectively. NO-mediated relaxations were reversibly blocked by 1 microM oxyhaemoglobin. The time course of NO-mediated relaxation comprised a delay of 3-7 s, followed by a sigmoidal decline in tension with peak rates that were strongly dependent on NO concentration.
Carter
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TD
National Institute for Medical Research, London.
Bettache
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N
Ogden
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D
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010782:Photolysis; D011817:Rabbits; D017975:Ruthenium Compounds / Q000737:chemistry*
D017975:Ruthenium Compounds; C110376:dipotassium pentachloronitrosylruthenate; C110377:trichloronitrosylruthenium; D009569:Nitric Oxide; D000109:Acetylcholine; D009638:Norepinephrine