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

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Abstract

In the present study, we investigate the inhibitory effect of novel H<inf>2</inf>S 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 H<inf>2</inf>S donors was studied on phenylephrine-induced tone in the absence or presence of enzyme inhibitors for the following pathways: cyclooxygenase (COX); H<inf>2</inf>S; nitric oxide and the ATP-sensitive K<sup>+</sup> (K<inf>ATP</inf>) channel. The H<inf>2</inf>S donors, NaSH (1nM - 10μM), AP67 (1nM - 10μM) and AP72 (10nM - 1μM) elicited a concentration-dependent relaxation of phenylephrine-induced tone in isolated bovine PCA. While the COX inhibitor, flurbiprofen (3μM) 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 (30μM) and propargylglycine (1mM), enzyme inhibitors of H<inf>2</inf>S biosynthesis caused significant (p<0.05) rightward shifts in the concentration-response curve to AP67 and AP72. Furthermore, the K<inf>ATP</inf> channel antagonist, glibenclamide (300μM) and the NO synthase inhibitor, l-NAME (100μM) significantly attenuated (p<0.05) the relaxation effect induced by AP67 and AP72 on PCA. We conclude that H<inf>2</inf>S donors can relax pre-contracted isolated bovine PCA, an effect dependent on endogenous production of H<inf>2</inf>S. The inhibitory action of only AP67 on pre-contracted PCA may involve the production of inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of H<inf>2</inf>S donors on PCA may depend on the endogenous biosynthesis of NO and by an action of K<inf>ATP</inf> channels.

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Kulkarni-Chitnis, M., Njie-Mbye, Y. F., Mitchell, L., Robinson, J., Whiteman, M., Wood, M. E., … Ohia, S. E. (2015). Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries. Experimental Eye Research, 134, 73–79. https://doi.org/10.1016/j.exer.2015.04.001

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