Open AccessChronic Nifedipine Treatment Diminishes Cardiac Inotropic Response to Nifedifine: Functional Upregulation of Dihydropyridine Receptors
Author(s) -
Gladys E. Chiappe de Cingolani,
Susana M. Mosca,
Abel E. Moreyra,
Horacio E. Cingolani
Publication year - 1996
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199602000-00010
Subject(s) - nifedipine , contractility , dihydropyridine , inotrope , medicine , nitrendipine , endocrinology , chemistry , cardiology , calcium
Chronic treatment with nifedipine induces up-regulation of functional active Ca2+ channels in cardiac muscle membranes. Adult male New Zealand White rabbits (NZW) were treated with nifedipine (20 mg/day) for 25 days. In isovolumic perfused hearts at constant coronary flow and heart rate (HR) the left ventricular developed pressure (LVDP) and its first derivative (dP/dt) were monitored. Basal contractility and contractility at different end-diastolic volumes (EDV) were higher in nifedipine-treated animals, with no changes in diastolic chamber stiffness. Dose response to nifedipine in pretreated animals showed less decrease in contractility than in controls [ED50 = 1.09 +/- 0.09 x 10-7 (control) and 1.55 +/- 0.17 x 10-7 M nifedipine (treated) (p < 0.05)]. Ca2+ channel density was assessed by specific binding at the dihydropyridine receptor with [methyl-3H]PN 200-110. In cardiac membranes, maximal binding capacity (Bmax) was 269 +/- 38 (n = 7, control) and 429 +/- 46 fmol/mg protein (n = 7, treated) (p < 0.05), without significant changes in dissociation constant. In addition, we noted no changes in dihydropyridine (DHP) binding sites in aortic membranes. Our results offer a possible explanation for the lack of decrease in contractility despite the persistent hypotensive effect in hypertensive patients during chronic treatment with nifedipine.