A New Role for Histamine H2-Receptors in Asthmatic Airways
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Histamine tachyphylaxis develops with repeated inhalation of histamine in asthmatic subjects, and this appears to be due to the release of inhibitory prostaglandins. The purpose of this study was to determine whether histamine H2-receptors are also involved in the development of this protective effect in the airways. Seven subjects with mild asthma were studied on 2 days separated by at least 1 wk. On both days, three histamine inhalation tests were performed, separated by 1 h. The response was expressed as the provocative concentration of histamine causing a 20% decrease in FEV1 (histamine PC20). Before each study day subjects were pretreated with placebo or cimetidine (300 mg twice a day) for 3 days in a double-blind, randomized, crossover study. Cimetidine pretreatment had no effect on either baseline FEV1 or on baseline histamine PC20 (p = 0.461). After pretreatment with placebo, histamine tachyphylaxis occurred in all subjects; the mean PC20 increased from 3.01 mg/ml (%SD, 1.44) to 4.88 mg/ml (%SD, 1.68) and to 6.84 mg/ml (%SD, 1.68). Cimetidine pretreatment prevented histamine tachyphylaxis; the mean PC20 was 2.72 mg/ml (%SD, 1.77), 3.03 mg/ml (%SD, 1.73), and 3.56 mg/ml (%SD, 1.59) with repeated tests. These values differed significantly from placebo for both the second (p = 0.014) and third (p = 0.001) tests. This study demonstrated that cimetidine pretreatment prevents histamine tachyphylaxis and suggests that histamine tachyphylaxis occurs through stimulation of histamine H2-receptors in the airway.