Affiliation:
1. From the Institut für Pharmakologie und Toxikologie, Technische Universität München, Germany.
Abstract
The role of T-type Ca
2+
channels for cardiovascular physiology, in particular blood pressure regulation, is controversial. Selective blockade of T-type Ca
2+
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 Ca
2+
channel Ca
v
1.2 (Ca
v
1.2
SMAKO
mice) to genetically dissect the effects of mibefradil on T- and L-type Ca
2+
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
v
1.2-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
v
1.2
SMAKO
mice. These results demonstrate that the effect of the putative T-type Ca
2+
channel-selective blocker mibefradil on blood pressure and small vessel myogenic tone is mediated by the Ca
v
1.2 L-type Ca
2+
channel.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
65 articles.
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