Effects of buflomedil on the responsiveness of canine vascular smooth muscle

Abstract

Experiments were designed to determine the effect of buflomedil on vascular responsiveness. Rings of canine arteries and veins were suspended for isometric tension recording at 37° C. Buflomedil caused concentration-dependent inhibition of the contractile responses to norepinephrine, methoxamine, phenylephrine, clonidine, xylazine and sympathetic nerve activation, but not of the responses to potassium, prostaglandin F(2α), acetylcholine or 5-hydroxytryptamine. The inhibitory effect of buflomedil was not afffected by endothelium removal but was reduced by chemical sympathectomy with 6-hydroxydopamine and by inhibitors of neuronal uptake. Strips of canine saphenous veins were superfused after incubation with [3H]norepinephrine. Buflomedil augmented the efflux of [3H]norepinephrine, 3,4-[3H]dihydroxyphenylglycol, 3,4-[3H]dihydroxymandelic acid and [3H]-3-methoxy-4-hydroxyphenylglycol under basal conditions and the overflow of [3H]norepinephrine, 3,4-[3H]dihydroxymandelic acid and 3,4-[3H]dihydroxyphenylglycol during sympathetic nerve activation. The augmentation by buflomedil of the release of [3H]norepinephrine evoked by electrical stimulation was prevented by phentolamine. In the perfused gracilis muscle of the anesthetized dog, buflomedil depressed the vasoconstrictor response to norepinephrine more than that evoked by angiotensin II. These experiments suggest that buflomedil blocks alpha adrenoceptors, but is not selective for either the alpha-1 or alpha-2 adrenoceptor subtype. The presence of adrenergic nerve endings appear to augment the postjunctional inhibitory effects of buflomedil.