Angiographic studies on the effects of a novel calcium antagonist AE0047 on cerebral arteries in dogs, with special reference to the preventive effects of AE0047 on cerebral vasoconstriction induced by endothelin

AE0047, a novel calcium antagonist, has mild and long-acting hypotensive effects. This drug also has more selective dilating action on cerebral arteries than on other systemic ones. We studied the cerebral vasodilatative effects of AE0047 by means of vertebral angiography in anesthetized dogs. Vertebral blood flow (VBF) was significantly increased by 91, 139 and 132% in 10, 30 and 60 min after intravenous administration of AE0047 at 30 micrograms/kg, respectively. No difference in vasodilating action was observed among basilar, posterior communicating, middle cerebral and internal carotid arteries. In basilar artery, the dilatative rate was about 30% between 10 and 60 min after injection of AE0047. Following intravertebral administration of endothelin at 100 pmol/kg, small vessels of the cerebral artery were constricted, and VBF was gradually decreased. AE0047 eliminated the vasoconstriction and increased VBF. Moreover, the vasoconstrictive effect of endothelin was prevented by pre-treatment of AE0047. These results indicate that AE0047 has potent vasodilating and spasmolytic actions on cerebral arteries.