title: Comparative effects of mibefradil and other calcium antagonists on resistance arteries of different end organs.
abstract: 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.
authors.affiliation: Department of Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van der Lee
authors.forename: M
authors.initials: M
authors.lastname: Pfaffendorf
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D020748:Mibefradil; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D013764:Tetrahydronaphthalenes; D020748:Mibefradil