CARDIOVASCULAR STUDIES ON VENOM FROM THE SOLDIERFISH (GYMNAPISTES MARMORATUS)

This study examined some of the effects of soldierfish (Gymnapistes ma rmoratus) venom on the cardiovascular system of rats. Venom (20 mu g/m l) produced a biphasic response on rat isolated spontaneously beating atria. This was characterised by a negative, followed by a positive, i notropic and chronotropic action. The increase in force and rate was s ignificantly reduced by propranolol (5 mu M) or pretreatment of the ra ts with reserpine. The decrease in force was significantly inhibited b y atropine (0.5 mu M). Venom (20-60 mu g/ml) produced dose-dependent r elaxation in rat isolated endothelium-intact aortae but no response in endothelium-denuded aortae. Relaxation to venom (30 mu g/ml) was sign ificantly inhibited by the nitric oxide synthase inhibitor N omega-nit ro-L-arginine (NOLA; 0.1 mM) but was unaffected by atropine (0.5 mu M) . Venom (200 mu g/kg, i.v.) produced a biphasic response in anaestheti zed rats, consisting of an initial decrease (phase 1) followed by a pr olonged increase (phase 2) in mean arterial pressure. Indomethacin (5 mg/kg, i.v.) significantly inhibited phase I of the response to venom and significantly potentiated phase 2. NOLA (30 mg/kg, i.v.) significa ntly inhibited phase 1 of the response to venom and had no significant effect on phase 2. Propranolol (0.5 mg/kg, i.v.) had no significant e ffect on phase 1 of the response to venom but significantly potentiate d phase 2. Neither phase of the response to venom was significantly af fected by atropine (2 mg/kg, i.v.), methysergide (2 mg/kg, i.v.) or pr azosin (50 mu g/kg, i.v.). These results suggest that soldier fish ven om acts indirectly at mu-adrenoceptors to produce a positive inotropic and chronotropic effect in atria. and acts at muscarinic receptors to produce a negative inotropic effect.. In addition, mu-adrenoceptors m ediate a delayed depressor component in vivo that is absent throughout the initial depressor response to the venom and present during, but m asked by, the presser response. Soldierfish venom also appears to stim ulate the release of nitric oxide from endothelial cells to produce re laxation of vascular smooth muscle and contribute to the depressor res ponse produced by the venom in anaesthetized rats. The depressor respo nse also appears to be partially mediated by vasodilator prostanoids. (C) 1998 Elsevier Science Ltd. All rights reserved.