Harris A L, Grant A M, Silver P J, Evans D B, Alousi A A
Department of Pharmacology, Sterling-Winthrop Research Institute, Rensselaer, New York 12144.
J Cardiovasc Pharmacol. 1989 Feb;13(2):238-44. doi: 10.1097/00005344-198902000-00010.
The vasorelaxant effects of milrinone and amrinone in canine coronary, cerebral, and renal arterial rings or strips contracted by either K+-depolarization, U46619 (a thromboxane mimetic), or prostaglandin F2 alpha (PGF 2 alpha) were quantitated. Milrinone was more potent as a vasorelaxant in coronary arteries relative to cerebral or renal arteries regardless of the mode of contraction; amrinone was coronary selective with K+ contraction only. When comparing potency in arteries contracted by different agonists, milrinone was significantly more potent as a vasorelaxant in all three arteries contracted by either U46619 or PGF2 alpha than in arteries contracted by K+ depolarization, whereas amrinone was only selective for U46619-induced contractions in cerebral arteries. This profile of activity for milrinone was similar to that of sodium nitrite and isoproterenol and dissimilar from the calcium entry blocking agents nimodipine and nifedipine. In conclusion, this study shows that coronary vascular selectivity exists for milrinone and amrinone. Moreover, the relaxant profiles of milrinone and amrinone, with different sources of vascular smooth muscle, are unlike those of calcium entry blocking agents and more similar to the profiles of agents that modulate cyclic nucleotide levels.
对米力农和氨力农在由钾离子去极化、U46619（一种血栓素类似物）或前列腺素F2α（PGF2α）引起收缩的犬冠状动脉、脑动脉和肾动脉环或条带中的血管舒张作用进行了定量分析。无论收缩模式如何，米力农作为冠状动脉血管舒张剂相对于脑动脉或肾动脉更有效；氨力农仅在钾离子收缩时具有冠状动脉选择性。在比较不同激动剂引起收缩的动脉中的效力时，米力农在所有由U46619或PGF2α引起收缩的三条动脉中作为血管舒张剂的效力明显高于由钾离子去极化引起收缩的动脉，而氨力农仅对脑动脉中U46619诱导的收缩具有选择性。米力农的这种活性特征与亚硝酸钠和异丙肾上腺素相似，与钙通道阻滞剂尼莫地平和硝苯地平不同。总之，本研究表明米力农和氨力农存在冠状动脉血管选择性。此外，米力农和氨力农在不同血管平滑肌来源中的舒张特征与钙通道阻滞剂不同，更类似于调节环核苷酸水平的药物的特征。
