The effects of honey bee (Apis mellifera L.) venom and two of its constituents, melittin and phospholipase A2, on the cardiovascular system of the rat

The cardiovascular effects of whole lyophilised honey bee venom and its major constituents, melittin and phosphatidate 2-acylhydrolase, EC 3.1.1.4 (phospholipase A2) have been studied in the anaesthetised rat and on the isolated perfused rat heart. Single bolus injections of whole venom (5–20 μg) irreversibly paralysed the isolated heart in 30–60 sec; perfusion of lower concentrations (1–8 μg/g tissue/min) caused paralysis over longer periods. In the whole animal, bee venom produced two differing responses on blood pressure depending on resting levels. In animals with a mean blood pressure of 95/67 mmHg, venom (0·5 mg/kg body weight) caused an increase of about 20 mmHg in 30 sec; in animals with a mean blood pressure of 138/112 mmHg, venom (0·7 mg/kg body weight) caused a marked fall. In both cases blood pressure returned to pre-venom levels after 5 min. Electrocardiographic changes were noted 15–20 min after envenomation, principally T wave elevation followed by ST-segment depression. The majority of these effects can be ascribed to the main constituents of honey bee venom; melittin (20–40 μg) irreversibly paralysed the isolated heart in 37–64 sec, phospholipase A2 was inactive. In the anaesthetised animal, melittin (200 μg/kg) slightly increased blood pressure but did not invariably affect ECG, whereas phospholipase A2 was profoundly hypotensive. The cardiotoxicity of melittin was less marked in the whole animal.