The determination of beta-adrenoceptor antagonist cardioselectivity "in vivo": atenolol in anaesthetized cats.
A study has been carried out to establish the best method for determining the cardioselectivity of beta-adrenoceptor antagonists in vivo, exemplified by atenolol in the anaesthetized cat preparation. Using three beta-adrenoceptor agonists: terbutaline (beta 2), dobutamine (beta 1), and isoprenaline and monitoring atenolol's antagonism of the agonist effects on heart rate, airway elastance and soleus muscle tension, parallel shifts in dose-response curves for each agonist were observed on each parameter. The cardioselectivity of atenolol was determined with each agonist by comparison of DR10 values from Schild plots and mean dose-ratio shifts. It is concluded that the cardioselectivity of atenolol is best determined by comparing its antagonism of dobutamine (beta 1) on heart rate (beta 1) with its antagonism of terbutaline (beta 2) on soleus muscle tension (beta 2) or airway elastance (beta 2). Skeletal muscle is suggested as a better beta 2 adrenoceptor model than airways for use in cardioselectivity determinations.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D002415:Cats; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D013726:Terbutaline / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D004280:Dobutamine; D001262:Atenolol; D007545:Isoproterenol; D013726:Terbutaline