title: Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries.
abstract: In the present study, we investigate the inhibitory effect of novel H2S donors, AP67 and AP72 on isolated bovine posterior ciliary arteries (PCAs) under conditions of tone induced by an adrenoceptor agonist. Furthermore, we examined the possible mechanisms underlying the AP67- and AP72-induced relaxations. Isolated bovine PCA were set up for measurement of isometric tension in organ baths containing oxygenated Krebs solution. The relaxant action of H2S donors was studied on phenylephrine-induced tone in the absence or presence of enzyme inhibitors for the following pathways: cyclooxygenase (COX); H2S; nitric oxide and the ATP-sensitive K(+) (KATP) channel. The H2S donors, NaSH (1 nM - 10 μM), AP67 (1 nM - 10 μM) and AP72 (10 nM - 1 μM) elicited a concentration-dependent relaxation of phenylephrine-induced tone in isolated bovine PCA. While the COX inhibitor, flurbiprofen (3 μM) blocked significantly (p < 0.05) the inhibitory response elicited by AP67, it had no effect on relaxations induced by NaSH and AP72. Both aminooxyacetic acid (30 μM) and propargylglycine (1 mM), enzyme inhibitors of H2S biosynthesis caused significant (p < 0.05) rightward shifts in the concentration-response curve to AP67 and AP72. Furthermore, the KATP channel antagonist, glibenclamide (300 μM) and the NO synthase inhibitor, l-NAME (100 μM) significantly attenuated (p < 0.05) the relaxation effect induced by AP67 and AP72 on PCA. We conclude that H2S donors can relax pre-contracted isolated bovine PCA, an effect dependent on endogenous production of H2S. The inhibitory action of only AP67 on pre-contracted PCA may involve the production of inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of H2S donors on PCA may depend on the endogenous biosynthesis of NO and by an action of KATP channels.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
authors.forename: Madhura
authors.initials: M
authors.lastname: Kulkarni-Chitnis
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
authors.forename: Ya Fatou
authors.initials: YF
authors.lastname: Njie-Mbye
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Mitchell
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
authors.forename: Jenaye
authors.initials: J
authors.lastname: Robinson
authors.affiliation: University of Exeter Medical School, St. Luke's Campus, Magdalen Road, Exeter EX1 2LU, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Whiteman
authors.affiliation: Department of Biosciences, College of Life and Environmental Sciences, University of Exeter, UK.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wood
authors.affiliation: Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE 68178, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Opere
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA. Electronic address: ohiase@tsu.edu.
authors.forename: Sunny E
authors.initials: SE
authors.lastname: Ohia
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D019842:Ciliary Arteries / Q000187:drug effects / Q000502:physiology*; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007537:Isometric Contraction / Q000502:physiology; D054086:KATP Channels / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D012985:Software Design; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C000599418:AP67 compound; C000599419:AP72 compound; D058646:Adrenergic alpha-1 Receptor Agonists; D004791:Enzyme Inhibitors; D054086:KATP Channels; D009943:Organophosphorus Compounds; D010880:Piperidines; D011759:Pyrrolidines; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: Cystathionine β-synthase; Cystathionine γ-lyase; Hydrogen sulfide; K(ATP) channel; Nitric oxide; Ocular blood flow; Posterior ciliary artery
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