Cytosolic calcium and lymphoproliferative response during calcium antagonism in men.
OBJECTIVE
A double-blind, placebo-controlled parallel study was conducted on the effect of mibefradil, both an L- and T-type Ca2+-channel blocker with a more selective blockade of T-type channels, administered once daily for 1 week to normal male subjects, on blood pressure, intracellular cationic concentrations, sodium-proton exchange rate and 3H-thymidine incorporation in peripheral blood mononuclear cells (PBMC).


METHODS
After a 1-week run-in period on placebo, the subjects (n = 40) were allocated to a placebo or a mibefradil group. Placebo or 50 mg mibefradil was administered once daily in the morning for 1 week. All subjects were investigated at baseline and after 1 week of placebo or mibefradil administration. Standing or recumbent blood pressure and heart rate of subjects in the mibefradil group was decreased (P < 0.05 or less) compared with that of subjects in the placebo group.


RESULTS
Decreased (P < 0.001) intracellular free Ca2+ concentration and reduced (P < 0.001) 3H-thymidine incorporation in the PBMC were observed in the mibefradil-treated subjects. The intracellular sodium, potassium or magnesium concentration as well as the sodium-proton exchange rate were not changed during mibefradil administration.


CONCLUSIONS
The blood pressure lowering action of mibefradil in men is accompanied by a decrease in intracellular free Ca2+ concentration. Mibefradil also reduced the 3H-thymidine incorporation or de novo DNA synthesis in PBMC by modulating the calcium homeostasis.
Lijnen
P
P
Department of Molecular and Cardiovascular Research, KU Leuven, Belgium. paul.lijnen@med.kuleuven.ac.be
Fagard
R
R
Petrov
V
V
D000328:Adult; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007477:Ions; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020748:Mibefradil; D010919:Placebos; D011188:Potassium / Q000378:metabolism; D017494:Proton Pumps / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D007477:Ions; D010919:Placebos; D017494:Proton Pumps; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D012964:Sodium; D011188:Potassium; D002118:Calcium