The effects of honey bee ( Apis mellifera L.) venom and two of its constituents, melittin and phospholipase A 2, on the cardiovascular system of the rat

Abstract

The cardiovascular effects of whole lyophilised honey bee venom and its major constituents, melittin and phosphatidate 2-acylhydrolase, EC 3.1.1.4 (phospholipase A 2) 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 A 2 was inactive. In the anaesthetised animal, melittin (200 μg/kg) slightly increased blood pressure but did not invariably affect ECG, whereas phospholipase A 2 was profoundly hypotensive. The cardiotoxicity of melittin was less marked in the whole animal.