Clerici C, Macquin-Mavier I, Harf A
Laboratoire de Physiologie, INSERM U 296 and Service de Pharmacologie Clinique, Hôpital Henri Mondor, Créteil, France.
Eur Respir J. 1988 Jan;1(1):10-4.
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.
在豚鼠、正常受试者和哮喘患者中，已反复证实选择性β1受体阻滞剂会损害肺功能。在30只麻醉并机械通气的豚鼠中，研究了几种β受体阻滞剂（普萘洛尔（非选择性）、阿替洛尔（β1选择性）、IPS 339（β2选择性））对组胺诱导的支气管收缩的影响，测量了传导率和动态顺应性的变化。通过静态压力-容积曲线测量肺扩张性变化，更具体地评估了它们对仅存在β2肾上腺素能受体的外周肺的影响。阿替洛尔（1mg·kg-1）、IPS 339（2mg·kg-1）和普萘洛尔（2mg·kg-1）增强了组胺诱导的肺扩张性、传导率和动态顺应性的降低。这三个参数的降低幅度相同。阿替洛尔（1mg·kg-1）和普萘洛尔（2mg·kg-1）使肺扩张性降低的程度相同。相比之下，低剂量阿替洛尔（0.1mg·kg-1）虽然确实产生了显著的心脏β受体阻滞作用，但并未增强组胺诱导的支气管收缩。这些结果表明：1）β受体阻滞剂对外周肺有明显影响；2）β1肾上腺素能受体不参与心脏选择性药物的肺部效应。研究结果提示，剂量依赖性选择性丧失是此类药物导致肺功能损害的主要机制。
