Vasorelaxant effect of trapidil on human basilar artery

We have investigated the vasorelaxant effect of trapidil on human isolated basilar artery. Trapidil (10(-5)-10(-4) M) dose-dependently caused relaxation in vascular strips with or without endothelium, with no significant difference between the two types of strips. The relaxation responses were not inhibited by atropine, propranolol or methylene blue. Trapidil increased the concentration of 6-keto-PGF1 alpha, a prostacyclin degradation product, released from an artery ring in the incubation medium, but trapidil-induced relaxation was not inhibited by indomethacin. Pretreatment of vascular strips with 10(-5) M trapidil increased the relaxation responses to forskolin and dibutyryladenosine cyclic monophosphate but not to sodium nitroprusside or 8-bromoguanosine cyclic monophosphate. Trapidil induced a significant increase in the cAMP concentration but not in the cGMP concentration in artery strips. These results suggest that the relaxation response to trapidil is not caused by prostacyclin release or an increase in cGMP in the smooth muscle, but possibly by an increase in the cAMP levels, probably via an inhibitory effect on cAMP phosphodiesterase.