Effects of cardioselective beta blockade on the peripheral lung in guinea pigs.
Impairment of lung function with selective beta-1 blocking drugs has been repeatedly demonstrated in guinea pigs, normal subjects and asthmatic patients. The effects of several beta blockers, propranolol (non-selective), atenolol (beta-1 selective), IPS 339 (beta-2 selective) on histamine-induced bronchoconstriction have been investigated in 30 anaesthetized and mechanically ventilated guinea pigs, measuring changes in conductance and dynamic compliance. Their effects on peripheral lung, where only beta-2 adrenoceptors are present, were more specifically assessed using changes in lung distensibility by means of static pressure-volume curves. Atenolol (1 mg.kg-1), IPS 339 (2 mg.kg-1) and propranolol (2 mg.kg-1) enhanced histamine-induced decrease in lung distensibility, conductance and dynamic compliance. The decrease was of the same order of magnitude for all three parameters. Atenolol (1 mg.kg-1) and propranolol (2 mg.kg-1) decreased lung distensibility to the same extent. By contrast low dose atenolol (0.1 mg.kg-1) did not potentiate histamine-induced bronchoconstriction although this dose did produce a significant cardiac beta blockade. These results demonstrate that 1) beta blockers have a clear effect on the peripheral lung, 2) beta-1 adrenoceptors are not involved in pulmonary effects of cardioselective drugs. They suggest that dose dependent loss of selectivity is the major mechanism behind impairment of lung function following such drugs.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008170:Lung Compliance / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D001262:Atenolol; C014898:IPS 339; D006632:Histamine; D011433:Propranolol; D007545:Isoproterenol