Benidipine, a dihydropyridine L-type/T-type calcium channel blocker, affords additive benefits for prevention of cardiorenal injury in hypertensive rats.
OBJECTIVE
Benidipine is a dihydropyridine calcium channel blocker inhibiting not only L-type but also T-type calcium channels. To elucidate potential additive benefit of benidipine for prevention of cardiorenal injury, we compared the cardiac and renal protective effects of equihypotensive doses of benidipine and cilnidipine in stroke-prone spontaneously hypertensive rats (SHRSP).


METHODS
SHRSP were divided into five groups, and were given vehicle, benidipine at 1 or 3 mg/kg per day, or cilnidipine at 1 or 3 mg/kg per day for 7 weeks, and the protective effects against cardiorenal injury were compared among each group.


RESULTS
Benidipine and cilnidipine at the same doses exerted comparable hypotensive effects on SHRSP throughout the treatment. Despite equihypotensive effects between both drugs, benidipine prevented cardiac hypertrophy, fibrosis, and inflammation to a greater extent than cilnidipine. Moreover, benidipine prevented glomerulosclerosis, tubulointerstitial injury, and renal inflammation more than cilnidipine. To elucidate the underlying mechanism of more beneficial effects of benidipine than cilnidipine, we compared the effects of these drugs on cardiac and renal oxidative stress, and aldosterone in SHRSP. Benidipine reduced both cardiac and renal NADPH oxidase activities in SHRSP more than cilnidipine, being associated with more attenuation of cardiac and renal superoxide by benidipine. Furthermore, serum aldosterone was significantly reduced by benidipine but not by cilnidipine.


CONCLUSIONS
Benidipine exerted more protective effects against cardiorenal injury of hypertensive rats than cilnidipine, through more attenuation of oxidative stress than cilnidipine, and the reduction of aldosterone. Benidipine, via blockade of T-type calcium channels, seems to elicit additive benefits for prevention of hypertensive cardiorenal injury.
Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Honjyo, Kumamoto, Japan.
Eiichiro
E
Yamamoto
Keiichiro
K
Kataoka
Yi-Fei
YF
Dong
Taishi
T
Nakamura
Masaya
M
Fukuda
Hisato
H
Nako
Hisao
H
Ogawa
Shokei
S
Kim-Mitsuyama
D000818:Animals; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate; D006973:Hypertension / Q000150:complications*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C061004:benidipine