NORADRENALINE REDUCES CARDIOVASCULAR EFFECTS OF THE COMBINED DIPYRIDAMOLE AND AMP ADMINISTRATION BUT PRESERVES RADIOPROTECTIVE EFFECTS OF THESE DRUGS AN HEMATOPOIESIS IN MICE

Recent results of the authors have demonstrated that the elevation of extracellular adenosine induced by the combined administration of dipy ridamole, a drug inhibiting the cellular uptake of adenosine, and aden osine monophosphate (AMP), a soluble adenosine prodrug, mediates radio protective effects in mice. Furthermore, it has been shown that this a ction is induced by at least two mechanisms: (1) protection by hypoxia as a result of the effects of treatment on the cardiovascular system (bradycardia, vasodilation), and (2) an enhanced regeneration of the r adiation-perturbed hematopoiesis. Here, it was ascertained that the jo int use of an optimal dose of noradrenaline given with dipyridamole an d AMP combination eliminates the hypothermic and hypoxic effects of th e treatment, but preserves the radioprotective action of dipyridamole and AMP combination in terms of hematopoietic recovery and partially a lso survival enhancing effects of the drugs in gamma-irradiated mice. These findings might be of importance for attempts to obtain available and tolerable radioprotective pharmacological prescriptions for clini cal use.