Evidence for cardiac beta 2-adrenoceptors in man.
We compared the effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective), and placebo on both exercise- and isoproterenol-induced tachycardia in two experiments involving nine normal subjects. Maximal exercise heart rate was reduced from 187 +/- 4(SEM) after placebo to 146 +/- 7 bpm after atenolol and 138 +/- 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0.04 mg/kg IV). Isoproterenol sensitivity was determined as the intravenous dose that increased heart rate by 25 bpm (CD25) and this was increased from 1.8 +/- 0.3 micrograms after placebo to 38.9 +/- 8.3 micrograms after propranolol and 8.3 +/- 1.7 micrograms after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2.3 +/- 0.3 micrograms) and atenolol (7.7 +/- 1.3 micrograms); it was reduced after propranolol (24.8 +/- 5.0 micrograms), but remained different from atenolol. This change with propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11.7 +/- 2.1 and 10.1 +/- 2.5 ml/ng). These data are consistent with the hypothesis that exercise-induced tachycardia results largely from beta 1-receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both beta 1- and beta 2-receptors so that after cardioselective blockade there remains a beta 2-component that can be blocked with a nonselective drug. While there appear to be beta 2-receptors in the human heart, their physiologic or pathologic roles remain to be defined.
D000328:Adult; D001262:Atenolol / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D005082:Physical Exertion; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000097:blood / Q000494:pharmacology*; D011897:Random Allocation; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011412:Propanolamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D011433:Propranolol; D007545:Isoproterenol