Dorigo P, Gaion R M, Bergamin M, Giacometti A, Valentini E, Maragno I
Department of Pharmacology, University of Padua, Padova, Italy.
Cardiovasc Drugs Ther. 1990 Dec;4(6):1477-85. doi: 10.1007/BF02026495.
Muzolimine (10-500 microM) induced a concentration-dependent reduction of both the contractile force and frequency in spontaneously beating atria and in electrically driven left atrium from reserpine-treated guinea pigs. This negative inotropic response was unaffected by the addition of atropine to the perfusion fluid, and it was highly sensitive to changes in external Ca2+ concentration. Both in spontaneously beating and in electrically driven atrium, muzolimine (50-400 microM) antagonized, in an apparently competitive manner, the increase in contractile force induced by cumulative addition of CaCl2 (0.68-9.59 mM) to the bathing fluid. Muzolimine (50-100 microM) reduced the inotropic response to low (5-30 nM), but not high (50-100 nM) concentrations of Bay K 8644, a calcium-channel agonist. The inotropic effects of 8-phenyltheophylline and of ouabain were antagonized by muzolimine (10-100 microM) in a noncompetitive manner, while the response to noradrenaline was not altered. Similar to muzolimine, verapamil at a concentration suitable to block calcium channels inhibited, in a noncompetitive way, the inotropic effect induced by 8-phenyltheophylline and by ouabain without altering the contractile response to noradrenaline. Furosemide (10 and 100 microM) did not influence the contractile force or the frequency of spontaneously beating atria, nor the inotropic effect induced by CaCl2, 8-phenyltheophylline, ouabain, or noradrenaline. These results indicate that the influence of muzolimine on guinea-pig atria originates from an inhibition of Ca2+ influx into cardiac cells and that furosemide does not mimic the effect of muzolimine at this level.
莫唑胺（10 - 500微摩尔）可使利血平处理的豚鼠自发搏动心房和电驱动左心房的收缩力和频率呈浓度依赖性降低。这种负性肌力反应不受向灌注液中添加阿托品的影响，且对外界钙离子浓度变化高度敏感。在自发搏动和电驱动心房中，莫唑胺（50 - 400微摩尔）均以明显竞争性方式拮抗向浴液中累积添加氯化钙（0.68 - 9.59毫摩尔）所诱导的收缩力增加。莫唑胺（50 - 100微摩尔）可降低对低浓度（5 - 30纳摩尔）而非高浓度（50 - 100纳摩尔）钙通道激动剂Bay K 8644的正性肌力反应。8 - 苯基茶碱和哇巴因的正性肌力作用被莫唑胺（10 - 100微摩尔）以非竞争性方式拮抗，而对去甲肾上腺素的反应未改变。与莫唑胺相似，浓度适宜以阻断钙通道的维拉帕米以非竞争性方式抑制8 - 苯基茶碱和哇巴因诱导的正性肌力作用，而不改变对去甲肾上腺素的收缩反应。呋塞米（10和100微摩尔）不影响自发搏动心房的收缩力或频率，也不影响氯化钙、8 - 苯基茶碱、哇巴因或去甲肾上腺素诱导的正性肌力作用。这些结果表明，莫唑胺对豚鼠心房的影响源于抑制钙离子流入心肌细胞，且呋塞米在此水平上不模拟莫唑胺的作用。
