Although recent clinical studies have suggested that long-acting
calcium channel blockers (CCBs) have beneficial effects on
heart failure, the precise mechanism is unknown. In this study, Dahl salt-sensitive rats fed a high
salt diet were treated with the long-acting CCB
amlodipine, the low-molecular-weight membrane permeable
superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (
Tempol), or saline from 11 weeks after birth. The cardiac geometry and function, and gene expression profiles were determined
at 17 weeks. Dahl salt-sensitive rats fed a high
salt diet followed by saline as a non-treatment control (HS group) showed a marked increase in blood pressure and developed concentric
hypertrophy at 11 weeks, followed by left ventricular (LV) dilation and
congestive heart failure by 17 weeks. The treatment with
amlodipine (AMLO group) or
Tempol (TEMP group) significantly inhibited the development of LV
hypertrophy and cardiac dysfunction. Analysis using an Affymetrix GeneChip U34 revealed that the expression levels of 195 genes were changed by the treatment with
amlodipine. Among these 195 genes, 110 genes were increased in HS rats and decreased in AMLO rats. And of these 110 genes, 54 genes were also decreased in TEMP rats. In contrast, 85 genes were decreased in HS rats and increased in AMLO rats. Of these 85 genes, 38 genes were also increased in TEMP rats. Approximately 48% of the genes were changed in similar fashion in AMLO and TEMP rats, suggesting that
amlodipine shows beneficial effects on
heart failure mainly via antioxidative mechanisms.