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.