Koga Y, Iwatsuki N, Hashimoto Y
Anesthesiology. 1987 Feb;66(2):181-5. doi: 10.1097/00000542-198702000-00012.
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 (greater than or equal to 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.
由于有人提出组胺H2受体拮抗剂可能会使哮喘患者的气道收缩恶化，我们研究了三种组胺H2受体拮抗剂对豚鼠气管平滑肌的体外比较作用。当针对静息张力进行测试时，西咪替丁、雷尼替丁和法莫替丁产生了剂量相关的舒张作用，其pD2值（舒张作用的ED50的负对数）（±SE，n；等于5）分别为3.20±0.04、2.95±0.16和2.97±0.14。低于舒张阈值的浓度不会引起收缩。然而，当制剂用组胺（10⁻⁵M）预收缩时，舒张的剂量反应曲线向右移动，并且所有三种组胺H2拮抗剂的低浓度都会增强组胺诱导的张力。当制剂用西咪替丁（10⁻⁶至10⁻⁴M）预处理，然后测试对组胺的敏感性时，组胺诱导收缩的剂量反应曲线向左移动（增强）。这些结果为气道H2受体对组胺收缩反应的调节作用提供了进一步的证据。此外，由于所有三种H2受体拮抗剂与组胺诱导收缩增强相关的浓度大致相同（大于或等于10⁻⁵M），我们的研究表明，必须以更高临床剂量给药的效力较低的H2受体拮抗剂导致气道收缩的可能性更大。
