A comparison of pre- and postsynaptic effects of α-adrenolytic drugs in the pulmonary artery of the rabbit

Abstract

Strips of the main pulmonary artery of the rabbit were preincubated with [ 3H]noradrenaline and then superfused and electrically stimulated transmurally. Yohimbine, dihydroergotamine and tolazoline at low concentrations enhanced the stimulation-evoked overflow of tritium; up to one hundred times higher concentrations were needed in order to reduce stimulation-evoked contractions. Piperoxan and mianserin enhanced the evoked overflow and reduced the evoked contractions at identical concentrations. Phentolamine, azapetine, clozapine and phenoxybenzamine at low concentrations diminished the contractile response; up to thirty times higher concentrations were needed to increase the evoked overflow of tritium. At high concentrations, all drugs accelerated basal tritium outflow. Separation of individual [ 3H]-compounds revealed that a high concentration of piperoxan markedly accelerated the basal outflow of [ 3H]3,4-dihydroxyphenylglycol. Lower concentrations of piperoxan and yohimbine that did not affect the basal efflux of [ 3H]-compounds greatly increased the evoked overflow of [ 3H]noradrenaline as well as of [ 3H]3,4-dihydroxyphenylglycol and [ 3H]normetanephrine. The pulmonary artery contains postsynaptic α-adrenoceptors which mediate smooth muscle contractions. Its noradrenergic neurones possess presynaptic α-receptors which mediate inhibition of the per pulse release of noradrenaline by a negative feedback mechanism. α-Adrenolytic drugs vary widely in their relative pre- and postsynaptic effects. Yohimbine, dihydroergotamine and tolazoline preferentially block presynaptic α-receptors and at low concentrations selectively facilitate noradrenaline release. Phentolamine, azapetine, clozapine and phenoxybenzamine preferentially block postsynaptic α-receptors and at low concentrations selectively antagonize the contractile response. Piperoxan and mianserin occupy an intermediate position. In a given tissue, pre- and postsynaptic α-receptors may differ in their structure.