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Long‐term blockade of L/N‐type Ca 2+ channels by cilnidipine ameliorates repolarization abnormality of the canine hypertrophied heart
Author(s) -
Takahara A,
Nakamura Y,
Wagatsuma H,
Aritomi S,
Nakayama A,
Satoh Y,
Akie Y,
Sugiyama A
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00407.x
Subject(s) - amlodipine , medicine , candesartan , qt interval , repolarization , angiotensin ii , endocrinology , cardiology , blood pressure , electrophysiology
Background and purpose: The heart of the canine model of chronic atrioventricular block is known to have a ventricular electrical remodelling, which mimics the pathophysiology of long QT syndrome. Using this model, we explored a new pharmacological therapeutic strategy for the prevention of cardiac sudden death. Experimental approach: The L‐type Ca 2+ channel blocker amlodipine (2.5 mg·day −1 ), L/N‐type Ca 2+ channel blocker cilnidipine (5 mg·day −1 ), or the angiotensin II receptor blocker candesartan (12 mg·day −1 ) was administered orally to the dogs with chronic atrioventricular block for 4 weeks. Electropharmacological assessments with the monophasic action potential (MAP) recordings and blood sample analyses were performed before and 4 weeks after the start of drug administration. Key results: Amlodipine and cilnidipine decreased the blood pressure, while candesartan hardly affected it. The QT interval, MAP duration and beat‐to‐beat variability of the ventricular repolarization period were shortened only in the cilnidipine group, but such effects were not observed in the amlodipine or candesartan group. Plasma concentrations of adrenaline, angiotensin II and aldosterone decreased in the cilnidipine group. In contrast, plasma concentrations of angiotensin II and aldosterone were elevated in the amlodipine group, whereas in the candesartan group an increase in plasma levels of angiotensin II and a decrease in noradrenaline and adrenaline concentrations were observed. Conclusions and implications: Long‐term blockade of L/N‐type Ca 2+ channels ameliorated the ventricular electrical remodelling in the hypertrophied heart which causes the prolongation of the QT interval. This could provide a novel therapeutic strategy for the treatment of cardiovascular diseases.