cyclic-gmp and 2-(nitrooxy)ethyl-apovincaminate

We investigated the effects of VA-045, an apovincaminic acid derivative, on isolated blood vessels. VA-045 (10(-7)-10(-5) M) and vinpocetine (10(-7)-10(-5) M) inhibited the 64 mM KCl-induced and 10(-6)M norepinephrine (NE)-induced contraction of rat aortic strips. VA-045 (10(-7)-10(-4) M) and vinpocetine (10(-7)-10(-4) M) inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterase in porcine coronary artery. VA-045 (3 x 10(-9-3 x 10(-6) M) relaxed the 64 mM KCl-induced contraction of the canine basilar artery without affecting the peripheral arteries. These results indicate that VA-045 selectively dilates canine cerebral artery, and that it may be a useful agent for the treatment of cerebrovascular diseases such as stroke.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; 8-Bromo Cyclic Adenosine Monophosphate; Animals; Aorta; Basilar Artery; Blood Vessels; Cerebral Arteries; Coronary Vessels; Cyclic GMP; Dogs; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Potassium Chloride; Rats; Rats, Wistar; Sensitivity and Specificity; Vasodilator Agents; Vinca Alkaloids