Differential effects of nebivolol, atenolol and propranolol on heart rate and on bronchoconstrictor responses to histamine in the guinea-pig.
Changes in heart rate and in bronchomotor reactions to histamine as parameters for beta 1- and beta 2-adrenergic receptor blockade, respectively, were analyzed in anaesthetized, ventilated guinea-pigs after administration of propranolol, atenolol and nebivolol. Propranolol (0.04 to 0.63 mg/kg i.v., -15 min) produces a significant reduction of the resting heart rate (80.4 +/- 4.25 to 74.9 +/- 4.17% of premedication values; n = 8; p less than 0.05) and, at the same dose levels, a significant enhancement of the bronchoconstrictor responses to histamine (3 micrograms/kg i.v.) (129.1 +/- 6.3 to 167.7 +/- 11.2% of premedication values; n = 8; p less than 0.05). Atenolol (0.02 to 1.25 mg/kg i.v., -15 min) significantly reduces heart rates from 0.04 mg/kg on (79.4 +/- 2.6 to 69.3 +/- 3.2% of premedication value at 1.25 mg/kg; n = 8; p less than 0.05) and significantly enhances the pulmonary reaction to histamine from 0.63 mg/kg on (139.1 +/- 6.3% to 137 +/- 11.6% of premedication values at 1.25 mg/kg; n = 8; p less than 0.05), yielding a dissociation factor of 16 between the lowest cardiac active dose and the pulmonary active one. Nebivolol (0.08 to 2.5 mg/kg i.v., -15 min) significantly reduces heart rates from 0.125 mg/kg on (78 +/- 3.2% to 65.4 +/- 3.9% of premedication value at 2.5 mg/kg; n = 8; p less than 0.05) without significantly increasing pulmonary reactivity (132.2 +/- 5.4% of premedication values at 2.5 mg/kg; n = 8; p greater than 0.05), thus yielding a dissociation factor greater than 20 between cardiac-pulmonary active doses. The study demonstrates a substantial dissociation between the cardiac (beta 1-adrenoceptors) and pulmonary (beta 2-adrenoceptors) active doses of nebivolol and atenolol in comparison with propranolol in vivo.
De Clerck
F
F
Department of Haematology, Janssen Research Foundation, Beerse, Belgium.
Van Gorp
L
L
Loots
W
W
Janssen
P A
PA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D000068577:Nebivolol; D011433:Propranolol / Q000494:pharmacology*; D012129:Respiratory Function Tests
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D001262:Atenolol; D006632:Histamine; D011433:Propranolol