STONUSTOXIN - A HIGHLY POTENT ENDOTHELIUM-DEPENDENT VASORELAXANT IN THE RAT

Stonefish venom has been documented to cause marked hypotension and re spiratory difficulties in envenomed animals. Stonustoxin, a lethal pro tein recently isolated from the venom of the stonefish Synanceja horri da produced hypotension and, at concentrations above 20,ug/kg, death i n anaesthetized rats, with no observable effects on nerve-evoked twitc hes of the tibialis and diaphragm muscles. Stonustoxin (20-160 ng/ml) induced endothelium-dependent relaxations of rat thoracic aortae preco ntracted with noradrenaline. Higher concentrations induced relaxations followed by contractions. Methylene blue, haemoglobin and the specifi c NO-synthase inhibitor L-N(G)-nitro arginine methyl ester inhibited s tonustoxin-induced relaxations, while the cyclooxygenase inhibitor ind omethacin was without effect. The results of the present study show th at stonustoxin causes marked vasorelaxation of the rat isolated aorta, which appears to be due to the release of endothelium-derived relaxin g factor (probably nitric oxide or nitric oxide-yielding substances) f rom the vascular endothelium, and this may be responsible for the in v ivo hypotensive and lethal actions of stonustoxin and of stonefish ven om.