Vasodilating properties of beta‐adrenoceptor blockers with intrinsic sympathomimetic activity.

Abstract

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-t M) or potassium (127 mM).2 Isoprenaline induced concentration-dependent relaxation and this effect could be competitively antagonized by propranolol or sotalol.3 The P-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 3-adrenoceptor antagonists with intrinsic sympathomimetic activity is the result of 32-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.

Bucindolol Exerts Agonistic Activity on the Propranolol-Insensitive State of β1-Adrenoceptors in Human Myocardium

“…It was assumed that the ISA of xamoterol was responsible for this negative outcome. Celiprolol, a ␤-adrenoceptor antagonist with ␤ 2 -agonistic properties (Thulesius et al, 1982;Böhm et al, 1992), had no beneficial effect in chronic heart failure (Witchitz et al, 2000). These data suggest an unfavorable role of any agonistic property in heart failure.…”

Influence of two β‐adrenoceptor antagonists, propranolol and pindolol, on cold adaptation in the rat

“…Due to its intrinsic sympathomimetic activity, pindolol has been shown to act as a partial fiadrenoceptor agonist in other tissues as well as the heart, e.g. peripheral blood vessels (Thulesius et al, 1982), and its effects on blood lipids are probably also related to this partial agonist activity (Leren et al, 1982). The slight reducing effect of pindolol on IBAT hypertrophy observed here is indicative of a potent P-adrenoceptor blocking effect in this tissue.…”

Human Aortic Smooth Muscle Cells Containing Angiotensin II Type 1 Receptors

“…In contrast, propranolol relaxed isolated dog and pig coronary arteries precontracted by 30 or 127.7 mM KCl through inhibition of Ca 21 influx across the smooth muscle cell membrane (7). Pindolol also relaxed isolated human arteries (except coronary artery) and dog mesenteric arteries contracted by 40 or 127 mM KCl through the stimulation of ,3-adrenergic receptors (9,19). These discrepancies may be due to the differences of ex perimental conditions, e.g., the different concentrations of KC1.…”

“…Namely, pindolol dilated hu man arteries and veins (10,19) and dog mesenteric and femoral arteries (8,9). However, pindolol constricted monkey and dog coronary arteries either non-preconstrict ed or preconstricted by 20 mM KCl (refs.…”