Synergism between hydrogen sulfide (H2S) and nitric oxide (NO) in vasorelaxation induced by stonustoxin (SNTX), a lethal and hypotensive protein factor isolated from stonefish Synanceja horrida venom

Abstract Stonustoxin (SNTX) is a 148 kDa, dimeric, hypotensive and lethal protein factor isolated from the venom of the stonefish Synanceja horrida . SNTX (10–320 ng/ml) progressively causes relaxation of endothelium-intact, phenylephrine (PE)-precontracted rat thoracic aortic rings. The SNTX-induced vasorelaxation was inhibited by l - N G -nitro arginine methyl ester ( l -NAME), suggesting that nitric oxide (NO) contributes to the SNTX-induced response. Interestingly, d , l -proparglyglycine (PAG) and β-cyano- l -alanine (BCA), irreversible and competitive inhibitors of cystathionine-γ-lyase (CSE) respectively, also inhibited SNTX-induced vasorelaxation, indicating that H 2 S may also play a part in the effect of SNTX. The combined use of l -NAME with PAG or BCA showed that H 2 S and NO act synergistically in effecting SNTX-induced vasorelaxation.