Chronic administration of nifedipine induces upregulation of dihydropyridine receptors in rabbit heart.
In rabbits chronically pretreated with nifedipine (20 mg/day for 25 days), we demonstrate upregulation of Ca2+ channels in mammalian heart (maximal binding capacity = 222 +/- 14 and 421 +/- 55 fmol/mg protein for control and treated, respectively; P < 0.05) without significant changes in dissociation constant. No changes in calcium sensitivity or maximal force were detected by pretreatment with nifedipine in chemically skinned fibers. Cardiac contractility at different extracellular Ca2+ concentrations was similar in control and pretreated animals. This upregulation of Ca2+ channels in mammalian heart offers an explanation for the lack of significant negative inotropic effect after chronic administration of nifedipine.
Chiappe De Cingolani
G E
GE
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Mosca
S M
SM
Vila Petroff
M
M
Cingolani
H E
HE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type; D003285:Contractile Proteins / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D010477:Perfusion; D011817:Rabbits; D013997:Time Factors; D015854:Up-Regulation
D020746:Calcium Channels, L-Type; D003285:Contractile Proteins; D009124:Muscle Proteins; D009543:Nifedipine; D002118:Calcium