Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries

• Published in: Experimental eye research Vol. 134; pp. 73 - 79
• Main Authors: Kulkarni-Chitnis, Madhura, Njie-Mbye, Ya Fatou, Mitchell, Leah, Robinson, Jenaye, Whiteman, Matthew, Wood, Mark E., Opere, Catherine A., Ohia, Sunny E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2015
• Subjects: Adrenergic alpha-1 Receptor Agonists - pharmacology; Animals; Cattle; Ciliary Arteries - drug effects; Ciliary Arteries - physiology; Cystathionine beta-Synthase - antagonists & inhibitors; Cystathionine beta-Synthase - metabolism; Cystathionine gamma-Lyase - antagonists & inhibitors; Cystathionine gamma-Lyase - metabolism; Cystathionine β-synthase; Cystathionine γ-lyase; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Isometric Contraction - physiology; KATP channel; KATP Channels - metabolism; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - physiology; Nitric oxide; Nitric Oxide - metabolism; Ocular blood flow; Organophosphorus Compounds - pharmacology; Phenylephrine - pharmacology; Piperidines - pharmacology; Posterior ciliary artery; Pyrrolidines - pharmacology; Software Design; Vasoconstrictor Agents - pharmacology; Cystathionine γ-lyase; l-NAME; H2S; Cystathionine β-synthase; Hydrogen sulfide; AOAA; CSE; CBS; Ocular blood flow; Nitric oxide; PAG; Posterior ciliary artery; KATP channel; SAM; K(ATP) channel
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2015.04.001

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. •H2S donors can relax pre-contracted isolated bovine posterior ciliary arteries.•Prostanoids are involved in the inhibitory action of AP67 on pre-contracted isolated bovine ciliary arteries.•Relaxation induced by H2S donors are dependent on biosynthesis of H2S by cystathionine γ-lyase and cystathionine β-synthase.•The inhibitory action of H2S donors is dependent on the endogenous biosynthesis of NO and by an action of KATP channels.