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

The biphasic contractile responses of rat isolated mesenteric, renal, coronary and basilar small arteries to potassium-induced depolarization were investigated. The tonic phase is assumed to be exclusively the result of L-type 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 contractions the effects of the LCC antagonists nifedipine, diltiazem and verapamil were compared with those of the combined L- and TCC antagonist mibefradil. Small arteries (size 393.6 +/- 4.8 microns, n = 104) were dissected from the respective organs of male Wistar rats (300-350 g) and studied in an isometric wire myograph. The effects of increasing concentrations of the calcium antagonists on repetitive potassium-induced contractions were quantified by means of cumulative concentration-response curves. A comparison was made with mesenteric vessels of SHR and WKY for nifedipine and mibefradil. Nifedipine 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. With respect to the tonic response mibefradil was comparable to verapamil (IC50 = 19.6-178.9 nM). These findings indicate that the TCC blockade does not contribute to the vasodilator effect of mibefradil under the conditions investigated.