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Using isolated ring preparations of major arteries mainly of canine origin, we attempted to explore the mechanism of the vasodilating effect of naftidrofuryl oxalate (I) at the concentration of approximately 10 microM. 1) The resting tension of canine carotid, femoral, coronary, renal and basilar arteries were not affected by I. 2) A weak or no papaverine-like activity was noted on coronary, renal and basilar arteries contracted by KCl (25 mM) or U46619 (20 nM). Porcine endothelin (30 nM)-induced contraction in the basilar artery also showed no response to I. 3) I produced a relatively strong anti-serotonergic effect in the basilar and femoral arteries, and the minimum effective concentrations of I for pretreating these arteries were 0.3 and 0.1 microM, respectively. I failed, however, to affect 8-OH-DPAT-induced contraction of the basilar artery. 4) In a low concentration such as 1 nM, I was able to release the vasodilating factor from the carotid artery. 5) The oscillatory contractions which developed in the rat thoracic aorta with phenylephrine (10 microM) were not affected by I (approximately 0.1 microM). 6) Na oxalate (approximately 1 mM) produced none of the effects of I described in 2) approximately 4). Based on the results obtained, it is concluded that I would exert its vasodilating effect not only directly via an anti-serotonergic action but also indirectly via its secretagogue-like action.

Evaluation of the vasodilating effect of naftidrofuryl oxalate using isolated canine and rat artery preparations.