HEMODYNAMIC-EFFECTS OF EPIDERMAL GROWTH-FACTOR IN CONSCIOUS RATS AND MONKEYS

The therapeutic application of growth factors to human disease has bec ome closer to reality with the advent of faster means of synthesizing these molecules and novel drug delivery strategies. Epidermal growth f actor (EGF) belongs to a large family of molecules with the ability to modulate growth. Purified extracts of EGF have been used clinically t o modulate gastrointestinal secretion of hormones and accelerate heali ng. EGF is also reported to have both vascular smooth muscle contracti le and relaxing activity. Cardiovascular studies were performed with t he bioactive 48-amino acid fragment of human EGF in rodents and primat es to determine the effects of EGF on blood pressure and heart rate in conscious animals. Intravenous infusion of EGF induced an initial pre sser response in rats followed by a prolonged decrease in blood pressu re. In contrast, in monkeys, EGF had dose-related blood pressure-lower ing effects only; significant hypotension was observed at doses rangin g from 3 to 300 mu g/kg i.v. Hypotension was associated with modest ta chycardia in both species. To our knowledge, this is the first report of hemodynamic effects of EGF in primates, and it clearly documents th at the mitogenic role of growth factors such as EGF is but one aspect of their physiology.