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.