Comparative effects of mibefradil and other calcium antagonists on resistance arteries of different end organs

The biphasic contractile responses of rat isolated mesenteric, renal, coron ary and basilar small arteries to potassium-induced depolarization were inv estigated. The tonic phase is assumed to be exclusively the result of L-typ e calcium channel (LCC) activation, whereas in the generation of the phasic phase T-type calcium channels (TCC) may be involved. In order to evaluate whether TCC blockade has any influence on depolarization-induced contractio ns the effects of the LCC antagonists nifedipine, diltiazem and verapamil w ere compared with those of the combined L- and TCC antagonist mibefradil. S mall arteries (size 393.6 +/- 4.8 mu m, n = 104) were dissected from the re spective organs of male Wistar rats (300-350 g) and studied in an isometric wire myograph. The effects of increasing concentrations of the calcium ant agonists on repetitive potassium-induced contractions were quantified by me ans of cumulative concentration-response curves. A comparison was made with mesenteric vessels of SHR and WKY for nifedipine and mibefradil. Nifedipin e was the most potent compound in blocking both the phasic phase (reduction 66-77%) and the tonic phase (IC50 = 1.1-5.4 nM). The effect of mibefradil on the phasic response was comparable to that of verapamil and diltiazem. W ith respect to the tonic response mibefradil was comparable to verapamil (I C50 = 19.6-178.9 nM). These findings indicate that the TCC blockade does no t contribute to the vasodilator effect of mibefradil under the conditions i nvestigated. (C) Elsevier, Paris.