Vasodilating properties of beta-adrenoceptor blockers with intrinsic sympathomimetic activity

1 In vitro experiments have been performed using 33 preparations of human arteries and veins and 10 human umbilical artery preparations. Changes in the tone of helical strips of vasculature were recorded isometrically following contraction of the tissues by exposure to 5-hydroxytryptamine (10(-6)--10(-5) M) or potassium (127 mM). 2 Isoprenaline included concentration-dependent relaxation and this effect could be competitively antagonized by propranolol or sotalol. 3 The beta-adrenoceptor antagonists pindolol and celiprolol, both of which possess intrinsic sympathomimetic activity, produced concentration-dependent relaxations of arteries and veins but not of umbilical vessels. 4 The relaxation produced by pindolol or celiprolol could be antagonized but not abolished by pretreatment with propranolol or sotalol. 5 It is concluded that the vascular relaxation produced by beta-adrenoceptor antagonists with intrinsic sympathomimetic activity is the result of beta 2-adrenoceptor stimulation. In the case of pindolol the relaxant effects were seen at concentrations within the range encountered after administration of normal therapeutic doses suggesting that this effect may contribute to the haemodynamic responses to pindolol seen in man.