Dose-dependent cardiovascular and neuromuscular effects of stonefish (Synanceja trachynis) venom

There has been recent debate regarding the labile nature of stonefish venom s and the pharmacology of their breakdown products. The present study exami ned the cardiovascular and neuromuscular effects of lyophilised venom, and conducted a preliminary investigation of freshly milked venom. Lyophilised venom (20 mu g/ml) caused endothelium-dependent relaxation in rat aortae th at was abolished by atropine (0.1 mu M). In contrast, an endothelium-indepe ndent contractile response occurred in porcine coronary arteries. However, in the presence of atropine (10 nM), this became a relaxation response whic h was attenuated by the B-2 antagonist FR-173657 (0.1 mu M) or by a combina tion of idazoxan (1 mu M) and propranolol (1 mu M). In rat isolated atria, lyophilised venom (4 mu g/ml) caused a biphasic inotropic response consisti ng of an initial decrease, and then increase, in force which were attenuate d by atropine (0.5 mu M) and propranolol (5 mu M), respectively. The increa se in force produced by venom was unaffected by reserpine pre-treatment sug gesting a direct action at adrenoceptors. In the anaesthetised rat, lyophil ised venom (1-300 mu g/kg, i.v.) caused a dose-dependent depressor response , with a subsequent presser response at higher concentrations (30-300 mu g/ kg, i.v.). In the presence of atropine (1 mg/kg, i.v.), the depressor respo nse to venom was abolished, a transient presser response unmasked and the s econdary presser response augmented. In the additional presence of prazosin (50 mu g/kg, i.v.). the transient presser response was abolished and the s econdary presser response attenuated. Lyophilised venom had no significant effect on nerve-evoked (10 mu g/ml) or directly-evoked (100 mu g/ml) twitch es of the chick biventer cervicis muscle preparation. Milked venom (1 mu l/ ml) caused a biphasic response (i.e., an initial relaxation followed by con traction) in rat aortae, a contraction in porcine coronary arteries, comple te cessation of rat isolated atrial activity and markedly inhibited both ne rve-evoked and directly-evoked twitches of the chick biventer cervicis musc le preparation. In the anaesthetised rat, milked venom (15 mu l/kg, i.v.) c aused immediate cardiovascular collapse. It appears that the cardiovascular effects of stonefish venom are mediated by a dose-dependent action at musc arinic receptors and adrenoceptors. (C) 1999 Elsevier Science Ltd. All righ ts reserved.