Comparison of the effects of cilnidipine and amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats.
OBJECTIVE
The L/N-type calcium channel blocker (CCB) cilnidipine suppresses sympathetic nerve activity and has a superior renoprotective effect compared with L-type CCBs such as amlodipine. The cardioprotective action of cilnidipine has remained largely uncharacterized, however. We have now investigated the effects of cilnidipine, in comparison with amlodipine, on cardiac pathophysiology in rats with salt-sensitive hypertension.


METHODS
Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age were treated with vehicle (LVH group), amlodipine (3 mg/kg per day), or cilnidipine (3 mg/kg per day) from 7 to 11 weeks.


RESULTS
The salt-induced increase in SBP apparent in LVH rats was attenuated to a similar extent by treatment with amlodipine or cilnidipine. The two drugs also similarly inhibited the development of left ventricular (LV) hypertrophy. However, cilnidipine attenuated the increase in relative wall thickness as well as ameliorated LV perivascular and interstitial fibrosis and diastolic dysfunction to a greater extent than did amlodipine. In addition, cilnidipine treatment was associated with greater inhibition of cardiac oxidative stress, inflammation, and renin-angiotensin system (RAS) gene expression. The decrease in cardiac norepinephrine content apparent in LVH rats was similarly inhibited by both drugs.


CONCLUSIONS
Cilnidipine attenuated LV fibrosis and diastolic dysfunction as well as LV concentricity to a greater extent than did amlodipine in Dahl salt-sensitive rats. The superior cardioprotective action of cilnidipine is likely attributable, at least in part, to the greater antioxidant and anti-inflammatory effects associated with inhibition of cardiac RAS gene expression observed with this drug.
Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Miwa
M
Takatsu
Takuya
T
Hattori
Tamayo
T
Murase
Masafumi
M
Ohtake
Miki
M
Kato
Keigo
K
Nashima
Chieko
C
Nakashima
Keiji
K
Takahashi
Hiromi
H
Ito
Kazumi
K
Niinuma
Shizuka
S
Aritomi
Toyoaki
T
Murohara
Kohzo
K
Nagata
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003971:Diastole; D004095:Dihydropyridines / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D020303:Rats, Inbred Dahl; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; C065927:cilnidipine