Relaxation of Porcine Isolated Irides by Novel Hydrogen Sulfide‐Releasing Compounds

Abstract

PurposeWe have previously reported that hydrogen sulfide (H2S)‐releasing compounds can elicit relaxation of pre‐contracted ocular vascular and non‐vascular smooth muscles. In the present study, we compared the pharmacological actions of novel mitochondrial‐targeting H2S‐releasing compounds (AP39, AP123, and RT‐01) with those of ADT‐OH on pre‐contracted porcine isolated irides.MethodsIsolated porcine iris muscle strips were set up in organ baths containing oxygenated Krebs buffer solution maintained at 37° C and gassed with 95% O2 and 5% CO2. The muscle strips were set to an initial resting tension of 0.15 g and longitudinal isometric tension was recorded via a grass FT03 Force‐Displacement Transducers and analyzed using the PolyView computer software. Pharmacological actions of AP39, AP123 and RT‐01 were assessed in the presence of tone induced by submaximal concentrations of the muscarinic agonist, carbachol. The cyclo‐oxygenase inhibitor, flurbiprofen (10 μM) was added to Krebs buffer solution during the incubation period and was present for duration of the experiments. ADT‐OH was used as a positive control in experiments using AP39, AP123 and RT‐01 since it lacked the mitochondrial targeting moiety.ResultsAP39 (1 nM – 10 μM), RT‐01 (1 nM – 10 μM) and AP123 (1 nM – 10 μM) elicited concentration‐dependent relaxations of carbachol‐induced tone. The rank order of activity was as follows (IC50): AP39, 50 nM (n = 10); RT‐01, 100 nM (n = 4); and AP123, 300 nM (n = 4). Likewise, the non‐mitochondrial‐targeting H2S donor, ADT‐OH (1 nM – 10 μM) caused a concentration‐dependent relaxation of porcine irides with an IC50 of 50 nM (n = 8).ConclusionsWe conclude that both novel mitochondria‐targeting H2S‐releasing compounds and their control counterpart, ADT‐OH can elicit relaxation of isolated porcine irides. The mitochondrial storage sites of this gas may not be involved in the inhibitory response caused by H2S‐releasing compounds in the porcine iris smooth muscle.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.