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(Circulation Research. 2006;98:105.)
© 2006 American Heart Association, Inc.

Cellular Biology

Antihypertensive Effects of the Putative T-Type Calcium Channel Antagonist Mibefradil Are Mediated by the L-Type Calcium Channel Ca_v1.2

Sven Moosmang, Nicole Haider, Birgit Brüderl, Andrea Welling, Franz Hofmann

From the Institut für Pharmakologie und Toxikologie, Technische Universität München, Germany.

Correspondence to Dr Sven Moosmang, Institut für Pharmakologie und Toxikologie der Technischen Universität München, Biedersteiner Strasse 29, 80802 München, Germany. E-mail moosmang{at}ipt.med.tu-muenchen.de

The role of T-type Ca²⁺ channels for cardiovascular physiology, in particular blood pressure regulation, is controversial. Selective blockade of T-type Ca²⁺ channels in resistance arteries has been proposed to explain the effect of the antihypertensive drug mibefradil. In the present study, we used a third generation, time- and tissue-specific conditional knockout model of the L-type Ca²⁺ channel Ca_v1.2 (Ca_v1.2^SMAKO mice) to genetically dissect the effects of mibefradil on T- and L-type Ca²⁺ channels. Myogenic tone and phenylephrine-induced contraction in hindlimb perfusion experiments were sensitive to mibefradil in control mice, whereas the drug showed no effect in Ca_v1.2-deficient animals. Mean arterial blood pressure in awake, freely moving control mice was reduced by 38±2.5 mm Hg at a dose of 1.25 mg/kg bodyweight mibefradil, but not changed in Ca_v1.2^SMAKO mice. These results demonstrate that the effect of the putative T-type Ca²⁺ channel-selective blocker mibefradil on blood pressure and small vessel myogenic tone is mediated by the Ca_v1.2 L-type Ca²⁺ channel.

Key Words: calcium channel • T-type • L-type • mibefradil • blood pressure

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