Selectivity of the Intrinsic Sympathomimetic Activity of the β-Adrenergic Blocking Drug Bucindolol

Abstract

We studied the comparative effects of β-adrenergic blockade with propranolol (PROP) and bucindolol (BUC), a β-adrenergic agonist having both otadrenergic blocking properties and intrinsic sympathomimetic activity (ISA) on airway and cardiovascular responses, in 38 mongrel dogs in situ. Intravenous infusion of 0.6 μg/kg + 6 μg/kg/min BUC and 2.0 mg/kg + 20 μg/kg/min PROP caused identical shifts in the isoproterenol (ISO) EC₅₀ for chronotropic and hypotensive arterial blood pressure responses. After PROP administration, resting heart rate (HR) decreased from 188 ± 15 to 142 ± 12 beats/min (p < 0.02); BUC caused no decrease in HR. In contrast, the effects of BUC and PROP on mean arterial blood pressure response to ISO were similar. No change in bronchomotor tone was observed after bolus injection of either BUC or PROP. β-Adrenergic relaxation to ISO and α-adrenergic contraction to norepinephrine (NE) were studied simultaneously in tracheal and bronchial airways using chronotropically equivalent β-adrenoceptor blocking doses of PROP and BUC. Comparable inhibition of ISO-induced airway relaxation after contraction with 120 μg/kg/min i.v. serotonin was demonstrated in both PROP (n = 5) and BUC (n = 5) groups (p < 0.01 for doses >5 × 10⁻¹¹ mol/kg). Similarly, both BUC (n = 5) and PROP (n = 5) blocked β-adrenergic relaxation and caused identical α-adrenergic airway contraction to intravenous NE. We conclude that the ISA of the β-adrenergic blocking drug BUC can be demonstrated on the spontaneous rate of the heart but not on the activity of branchial smooth muscle. BUC neither augments ISO-induced relaxation nor inhibits NE-induced contraction of airways after effective chronotropic blockade.