Syunji Yokota (1), Yukiko Naito (1), Hiromichi Yoshida (1), Naoki Ohara
(1), Tomoko Adachi (2) and Hiroshi Narita (3)
(1) Laboratory of Applied Pharmacology, (2) Laboratory of Biological
Chemistry, Hatano Research Institute, Food and Drugs Safety Center, 729-5
Ochiai, Hadano, Kanagawa 257-8523, Japan
(3) Pharmaceutical Development Research Laboratory, Tanabe Seiyaku Co.,
Ltd., 2-2-50 Kawagishi, Toda, Saitama 335-8505, Japan
Abstract: The present study was performed to compare cardioprotective
effects of an angiotensin-converting-enzyme inhibitor, imidapril, and of
a Ca2+ channel antagonist, amlodipine, against the cardiac hypertrophy
in male spontaneously hypertensive rats (SHRs) at the established stage
of hypertension. Fifteen-week-old SHRs were given imidapril (2 and 5 mg/kg/day)
or amlodipine (10 mg/kg/day) by gavage for 8 weeks. Three hours after the
1st treatment, imidapril moderately reduced blood pressure without changing
heart rate, while amlodipine caused a marked reduction in blood pressure
accompanied by transient tachycardia. At the end of the treatments, ventricular
weight in the imidapril-treated groups was markedly lower, but that in the
amlodipine-treated group was only slightly lower than that in the vehicle-treated
group. Myocardial collagen content in the imidapril-treated group tended
to be decreased, and significant reduction was observed in the low-dose
group. In another experiment, the isolated heart of the imidapril-treated
animals demonstrated better cardiac compliance than that in the vehicle-treated
animals. In contrast, amlodipine failed to improve cardiac function. The
present results suggest that imidapril possesses advantageous effects to
prevent cardiac hypertrophy and deteriorated cardiac function in SHRs of
established stage of hypertension as compared with amlodipine.
Keywords: Imidapril, Amlodipine, Spontaneously hypertensive rat, Cardiac
hypertrophy, Cardiac function