EFFECT OF GINKGO-BILOBA EXTRACT (EGB-761) ON THE VASOSPASTIC RESPONSEOF MOUSE CUTANEOUS ARTERIOLES TO PLATELET ACTIVATION

The effect of intravenously administered Ginkbo biloba extract (EGb 76 1) on the vasospastic response to platelet activation has been assesse d using a cutaneous flap preparation in anaesthetized mice. Arterioles of the axillary artery were observed by intravital microscopy, and pl atelets were activated by topical application of ADP under two steady state conditions: normothermia (37 degrees C) and hypothermia (24 degr ees C). Responses of the cutaneous arterioles to stimulation by topica l application of a thromboxane agonist (U46619) were also compared in animals treated intravenously with EGb 761 or with a thromboxane synth esis inhibitor (U63557). ADP induced a 34% constriction of the arterio les in control animals. However, no arteriolar constriction occurred i n response to ADP in platelet-depleted animals (collagen-induced throm bocytopenia) or in animals treated with EGb 761 (60 mg/kg, i.v.). Expo sure of the arterioles to hypothermia (24 degrees C) for 10 min induce d constriction of 7-12% in all experimental groups of animals. Under t hese hypothermic conditions, either EGb 761 or thrombocytopenia abolis hed ADP-induced arteriolar constriction which was substituted by arter iolar dilation, indicating that EGb 761 can inhibit tile vasospasm tha t is produced by platelet activation. As topically applied U46619 (10( -5) M) induced arterioles constriction (about 22%) that was abolished by intravenous treatment with EGb 761, the extract appears to act dire ctly rather than as a thromboxane synthase inhibitor. Collectively, th ese findings indicate that platelet factors can play a significant rol e in cutaneous vasospasm, and that EGb 761, via an action on the throm boxane pathway, could be useful in treating Raynaud's phenomenon and o ther vascular disorders which involve increased thromboxane production .