title: Inhibition by sulfhydryl compounds of vascular relaxation induced by nitric oxide and endothelium-derived relaxing factor.
abstract: On rings of rabbit thoracic aorta precontracted with phenylephrine, L-cysteine (Cys) and dithiothreitol (DTT) (1-100 microM), but not glutathione (GSH), produced dose-dependent augmentation of contraction in endothelium-intact, but not in endothelium-denuded rings. The augmentation appeared to be due to inhibition of basally released endothelium-derived relaxing factor (EDRF), and was abolished by pretreatment with superoxide dismutase (SOD, 15 U/ml). At a high dose (1 mM), Cys and GSH produced transient, and DTT produced sustained endothelium-independent relaxation, not influenced by SOD. Cys and DTT (10 microM), but not GSH, produced a small but significant inhibition of acetylcholine-induced endothelium-dependent relaxation, and this inhibition was prevented by SOD. In a perfusion-bioassay system in which EDRF was released by acetylcholine from endothelium of a perfused segment of rabbit aorta, Cys and DTT (20 microM), but not GSH, infused into the perfusate between the segment and an endothelium-denuded bioassay ring, partially inhibited relaxation by the EDRF, but not when SOD was present. In organ chamber experiments, the large transient relaxation of endothelium-denuded rings produced by 75 nM nitric oxide (NO) was partially inhibited in a concentration-dependent manner by Cys, DTT and GSH (0.1-100 microM). Moderate relaxation by 15 nM NO was almost completely inhibited by each compound at 10 microM. The order of potency was Cys > DTT > GSH. Cystine, glutathione disulfide and alanine did not inhibit. Inhibition of NO-induced relaxation was largely attenuated by SOD.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, State University of New York, Health Science Center at Brooklyn.
authors.forename: L
authors.initials: L
authors.lastname: Jia
authors.forename: R F
authors.initials: RF
authors.lastname: Furchgott
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D013438:Sulfhydryl Compounds; D013481:Superoxides; D009569:Nitric Oxide; D000109:Acetylcholine