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

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-NG-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 H2S may also play a part in the effect of SNTX. The combined use of l-NAME with PAG or BCA showed that H2S and NO act synergistically in effecting SNTX-induced vasorelaxation.