Bunazosin, an α1-adrenoceptor blocker, differentially releases co-transmitters in dog mesenteric vessels

Abstract

The effects of bunazosin on the electrical and mechanical responses of smooth muscle cells elicited by exogenously applied noradrenaline (NA) and by perivascular nerve stimulation were studied in the isolated mesenteric artery and vein of the dog. NA (above 10 −7 M in the artery and above 3 × 10 −8 M in the vein) depolarized the membrane. Perivascular nerve stimulation evoked an excitatory junction potential (e.j.p.) and slow depolarization in both vessels. Bunazosin and prazosin inhibited the NA-induced depolarization and slow depolarization in the artery but not in the vein. The NA actions in the vein were inhibited by yohimbine. Bunazosin (above 10 −6 M) increased the amplitude of the e.j.p. but decreased the outflow of NA during nerve stimulation. The amplitude and conduction velocity of the compound action potential of perivascular nerves were inhibited by higher concentrations of bunazosin (above 10 −5 M). The results provide evidence that bunazosin has selective inhibitory actions at α 1-adrenoceptors. This drug exerted differential effects on the release of co-transmitters which generate the e.j.p. and the slow depolarization, as bunazosin increased the former and decreased the latter. This suggests that e.j.p. is generated by a substance other than NA.