Human vascular to cardiac tissue selectivity of L- and T-type calcium channel antagonists

摘要

Voltage-operated calcium channel(VOCC) antagonists are effective antihypertensive and antianginal agents but they also depress myocardial contractility. We compared four L-type calcium channel antagonists, felodipine, nifedipine, amlodipine and Verapamil and a relatively T-type selective calcium channel antagonist, mibefradil, on human and rat Isolated tissue assays to determine their functional vascular to cardiac tissue selectivity(V/C) ratio. The V/C ratio was calculated as the ratio of the IC_50 value of the antagonist that reduced (by 50/100) Submaximally contracted(K~+ 62 mM) human small arteries from the aortic vasa vasorum(Vascular, V) Mounted in a myograph and the IC_50 value of the antagonist that reduced (-)-isoprenaline (6 mM) Submaximally stimulated human right atrial trabeculae muscle (cardiac, C) mounted in organ chambers.