TY - JOUR
T1 - Chronic nifedipine treatment diminishes cardiac inotropic response to nifedifine
T2 - Functional upregulation of dihydropyridine receptors
AU - Chiappe de Cingolani, Gladys E.
AU - Mosca, Susana M.
AU - Moreyra, Abel E.
AU - Cingolani, Horacio E.
PY - 1996
Y1 - 1996
N2 - 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 (B(max)) 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.
AB - 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 (B(max)) 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.
KW - Calcium channels
KW - Dihydropyridine receptors
KW - Heart contractility
KW - Nifedipine treatment
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U2 - 10.1097/00005344-199602000-00010
DO - 10.1097/00005344-199602000-00010
M3 - Article
C2 - 8720423
AN - SCOPUS:9044242638
SN - 0160-2446
VL - 27
SP - 240
EP - 246
JO - Journal of cardiovascular pharmacology
JF - Journal of cardiovascular pharmacology
IS - 2
ER -