title: Potency and kinetics of nitric oxide-mediated vascular smooth muscle relaxation determined with flash photolysis of ruthenium nitrosyl chlorides.
abstract: 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.
authors.affiliation: National Institute for Medical Research, London.
authors.forename: T D
authors.initials: TD
authors.lastname: Carter
authors.forename: N
authors.initials: N
authors.lastname: Bettache
authors.forename: D
authors.initials: D
authors.lastname: Ogden
mesh_terms: 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*
chemical_list: D017975:Ruthenium Compounds; C110376:dipotassium pentachloronitrosylruthenate; C110377:trichloronitrosylruthenium; D009569:Nitric Oxide; D000109:Acetylcholine; D009638:Norepinephrine