Inhibitory action of hydrogen sulfide on muscarinic receptor-induced contraction of isolated porcine irides

Abstract We investigated the pharmacological actions of hydrogen sulfide (H 2 S) using sodium hydrosulfide (NaHS) and sodium sulfide (Na 2 S) as donors on isolated porcine irides in the presence of tone induced by muscarinic receptor stimulation. Furthermore, we also investigated the mechanism of action of H 2 S in this smooth muscle. Isolated porcine iris muscle strips were set up in organ baths and prepared for measurement of longitudinal isometric tension. The relaxant action of NaHS or Na 2 S on carbachol-induced tone was studied in the absence and presence of a K + -channel inhibitor and inhibitors/activators of enzymes of the biosynthetic pathways for H 2 S, prostanoid and nitric oxide production. In the concentration range, 10 nM to 100 μM, NaHS produced a concentration-dependent relaxation of carbachol-induced tone reaching a maximum of inhibition of 28% at 30 μM. The cyclooxygenase inhibitor, flurbiprofen (1 μM), enhanced relaxations induced by both NaHS and Na 2 S yielding IC 50 values of 7 μM and 70 μM, respectively. With exception of l -NAME (300 μM) inhibitors of cystathionine γ-lyase, propargylglycine, (PAG) (1 mM) and β-cyanoalanine, (BCA) (1 mM) and inhibitors of cystathionine β-synthase, aminooxyacetic acid (AOA) (30 μM) and hydroxylamine (HOA) (30 μM) caused significant ( P 2 S donor. The inhibitor of K ATP channel, glibenclamide (100 and 300 μM), blocked relaxations induced by NaHS. We conclude that the observed inhibitory action of NaHS and Na 2 S in isolated porcine irides is dependent on endogenous production of prostanoids and the biosynthesis of H 2 S by cystathionine γ-lyase and cystathionine β-synthase. Furthermore, relaxation induced by H 2 S is mediated, at least in part, by K ATP channels. Nitric oxide is not involved in the relaxation induced by this gas in the isolated porcine irides.