Jackowski J, Chapman G A, Abraham W M, Ahmed T
Division of Pulmonary Disease, University of Miami School of Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140.
Respiration. 1993;60(1):27-31. doi: 10.1159/000196169.
We compared the inhibitory effects of calcium channel blockers, gallopamil and verapamil on acetylcholine (Ach)-induced contractions of ovine tracheal muscle in vitro. Adult sheep were sacrificed and tracheal strips were obtained by cutting the single tracheal rings from the mid-trachea. Tracheal strips were suspended in Krebs-Henseleit solution and isometric tension measured upon stimulation with cumulative doses of Ach (10(-7) to 10(-4) M) without and after pretreatment with gallopamil (10(-7) to 10(-6) M) or verapamil (10(-6) to 10(-5) M). In untreated tissues, the mean concentration of Ach required to produce 50% of maximal response (EC50) was 4.3 x 10(-6) M Ach. Both gallopamil and verapamil inhibited the Ach-induced contractions of ovine tracheal smooth muscle, by shifting the dose-response curves to Ach to the right. EC50 Ach for gallopamil (10(-6) M) and verapamil (10(-6) M) was 2.6 x 10(-5) and 5.2 x 10(-6) M, respectively. Dose ratio defined as postantagonist EC50 Ach/control EC50 Ach, was 7.7 for gallopamil and 2.0 for verapamil. Thus, the inhibitory effect of gallopamil was approximately 4-fold more potent than that of verapamil. Gallopamil was 17-fold more potent than verapamil in relaxing precontracted tracheal strips. The dose of calcium antagonists required to produce 25% relaxation (EC25) of tracheal strips precontracted with 10(-4) Ach was 3.7 x 10(-5) M for verapamil and 2.2 x 10(-6) M for gallopamil. These results indicate that gallopamil is effective against Ach-induced contractions of ovine trachealis muscles, and is more potent than verapamil.
我们比较了钙通道阻滞剂加洛帕米和维拉帕米对体外培养的羊气管肌肉乙酰胆碱（Ach）诱导收缩的抑制作用。处死成年绵羊，从气管中部切下单个气管环获取气管条。将气管条悬挂于克雷布斯 - 亨塞尔特溶液中，在累积剂量的Ach（10⁻⁷至10⁻⁴ M）刺激下测量等长张力，刺激前及用加洛帕米（10⁻⁷至10⁻⁶ M）或维拉帕米（10⁻⁶至10⁻⁵ M）预处理后进行测量。在未处理的组织中，产生最大反应50%所需的Ach平均浓度（EC50）为4.3×10⁻⁶ M Ach。加洛帕米和维拉帕米均抑制Ach诱导的羊气管平滑肌收缩，使Ach的剂量 - 反应曲线右移。加洛帕米（10⁻⁶ M）和维拉帕米（10⁻⁶ M）作用下的Ach EC50分别为2.6×10⁻⁵ M和5.2×10⁻⁶ M。定义为拮抗剂后EC50 Ach/对照EC50 Ach的剂量比，加洛帕米为7.7，维拉帕米为2.0。因此，加洛帕米的抑制作用比维拉帕米强约4倍。加洛帕米在舒张预收缩的气管条方面比维拉帕米强17倍。使预先用10⁻⁴ Ach预收缩的气管条产生25%舒张（EC25）所需的钙拮抗剂剂量，维拉帕米为3.7×10⁻⁵ M，加洛帕米为2.2×10⁻⁶ M。这些结果表明，加洛帕米对Ach诱导的羊气管肌收缩有效，且比维拉帕米更有效。
