The selectivity of β‐adrenoceptor antagonists on isoprenaline‐induced changes in heart rate, blood pressure, soleus muscle contractility and airways function in anaesthetized cats

Abstract

1 The P-adrenoceptor antagonist activity of propranolol, metoprolol, atenolol and butoxamine in anaesthetized cats has been measured and compared with the activity of four synthetic phenylethanolamine derivatives. 2 The effects of isoprenaline on four parameters in the anaesthetized cat: heart rate, blood pressure, soleus muscle contractility and airway reactance, were measured and the modification of the isoprenaline dose-response relation by each of the antagonist drugs assessed. 3 Parallel shifts in log dose-response curves for isoprenaline were caused by propranolol for all parameters, by metoprolol and atenolol for each parameter except blood pressure, and butoxamine for each except soleus muscle and heart rate. 4 Selectivity of action of the antagonists between different organs was measured by comparing DR10 values, computed from isoprenaline dose-ratios. 5 Propranolol was the most potent antagonist and showed slight selectivity of action on soleus muscle compared with heart. Atenolol and metoprolol were approximately equipotent and were cardioselective at low doses only. Butoxamine was the least potent antagonist and possessed non-0-adrenoceptor effects on the parameters measured. 6 Each of the new compounds, 4'-bromo-2'-methyoxy-N-isopropyl phenylethanolamine, the 4'-chloro-and 4'-methyl analogues, and 4'-methoxy-N-t-butyl phenylethanolamine, was a potent antagonist but did not exhibit any selectivity of action.7 The results suggest no clear separation of P-adrenoceptors into Pl-and P2-subclasses in organs of the cat. There is no apparent separation of ,B-adrenoceptor-mediated effects on skeletal muscle and airways.

Low dose beta‐blocker prevents ovariectomy‐induced bone loss in rats without affecting heart functions

“…Consequently, the cardio‐selectivity of these agents remains unknown since the dose of the non‐selective β‐blockers is known to change depending of the dose. It has been described by several authors that propranolol exhibited a somewhat beta2‐selectivity and that there is an inverse relationship between selectivity and propranolol dose (Letts et al, 1983; Hallberg, 1987; Smith and Teitler, 1999). These two observations support our data, hypothesizing that at a low dose, propranolol may affect specifically β2‐adrenergic receptors whereas, at higher doses, either β1 or β2‐adrenergic receptors would be blocked.…”

cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

“…cyclic AMP; skeletal muscle; cell signaling; muscle regeneration; atrophy; protein kinase A ORIGINALLY DISCOVERED by Sutherland and Rall in liver homogenates in 1958 (218), adenosine 3=,5=-monophosphate (cyclic AMP, or cAMP) has since been intensively studied and is one of the best-characterized signaling molecules. In skeletal muscle, acute cAMP signaling has been implicated in regulation of glycogenolysis (213), contractility (32,83,84,88,138,234), sarcoplasmic calcium dynamics (58,147,184,204), and recovery from sustained contractile activity (44, 162). The net result of acute cAMP action on the order of minutes in skeletal muscle can generally be described as increased contractile force and rapid recovery of ion balance, especially during prolonged contractions.…”

Adrenergic Modulation of Erythropoiesis After Trauma

“…Beta-2 receptors are located in human bronchial smooth muscle cells, vascular smooth muscle cells and cardiac myocytes, albeit at a lower expression density compared to beta-1 receptors ( Brodde, 2008 ; Perez, 2021 ). While selective β-2 antagonists are not in clinical use in humans, a beta-2 blocking agent called butoxamine has been shown to decrease blood pressure and heart rate and increase airway resistance in animal studies ( Letts et al, 1983 ; Beiermeister et al, 2010 ).…”