{'fraction_non_alphanumeric': 0.04037854889589906, 'fraction_numerical': 0.027129337539432176, 'mean_word_length': 5.2687747035573125, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Direct Effects of H2-Receptor Antagonists on Airway Smooth Muscle and on Responses Mediated by H1- and H2-Receptors

Because it has been suggested that histamine H2-receptor antagonists may worsen airway constriction in asthmatic patients, we investigated the comparative effects of three histamine H2-receptor antagonists on guinea pig tracheal smooth muscle in vitro. When tested against resting tone, cimetidine, ranitidine and famotidine produced dose-related relaxation with pD2 values (negative log of ED50 for relaxation) (±SE, n; eq 5) of 3.20 ± 0.04, 2.95 ± 0.16 and 2.97 ± 0.14, respectively. Concentrations that were below threshold for relaxation, did not elicit contraction. However, when the preparations were precontracted with histamine (10-5 M), dose-response curves for relaxation were shifted to the right, and low-concentrations of all three histamine H2-antagonists augmented histamine-induced tone. When preparations were pretreated with cimetidine (10-6 to 10-4 M) and then tested for sensitivity to histamine, dose-response curves for histamine-induced contraction were shifted to the left (potentiated). These results provide further evidence for a modulatory effect of airway H2-receptors on the contractile response to histamine. In addition, since the concentrations associated with potentiation of histamine-induced contraction were about the same for all three H2-receptor antagonists (≥10-5 M), our studies suggest a greater likelihood of airway constriction for the less potent H2-receptor antagonists that must be administered in higher clinical doses.