The N- and L-type calcium channel blocker cilnidipine suppresses renal injury in dahl rats fed a high-sucrose diet, an experimental model of metabolic syndrome.
OBJECTIVE
The L/N-type calcium channel blocker (CCB) cilnidipine has been demonstrated to suppress progressive renal disease in a variety of experimental models, but the characteristic effects of N-type calcium channel blocking action on renal injury have not been examined in detail. Therefore, we investigated the beneficial effects of cilnidipine on renal injury in Dahl salt-sensitive (Dahl S) rats fed a high-sucrose diet (HSD), which mimics metabolic syndrome, and compared them with the effects of an L-type CCB, amlodipine.


METHODS
Male Dahl S rats were divided into groups with similar blood pressure at 8 weeks of age and fed an HSD. They received vehicle, cilnidipine or amlodipine for 27 weeks. At 35 weeks of age, urine and blood samples were collected for physiological analysis, and the kidneys were removed for histopathological evaluation.


RESULTS
Cilnidipine reduced albuminuria, glomerular hypertrophy, glomerular expression of ICAM-1, ED-1-positive cell infiltration and interstitial fibrosis compared with vehicle-treated rats. In contrast, amlodipine had no effect on these parameters. Urinary norepinephrine excretion, renal expression of renin mRNA and renal tissue levels of angiotensin II were increased only in the amlodipine-treated group.


CONCLUSIONS
Cilnidipine provided superior protection against renal damage compared with amlodipine in Dahl S rats given an HSD. The different effects between these two drugs may be partly explained by their different actions on the renal sympathetic nerve activity and the renin-angiotensin system through the N-type calcium channel blocking action.
Konda
Tomoyuki
T
Pharmaceutical Research Laboratories, Ajinomoto Co. Inc., Kawasaki, Japan. tomoyuki_konda@ajinomoto.com
Enomoto
Azusa
A
Matsushita
Junko
J
Takahara
Akira
A
Moriyama
Toshiki
T
D017311:Amlodipine / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020864:Calcium Channels, N-Type / Q000187:drug effects; D019422:Dietary Sucrose / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006977:Hypertension, Renal / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D020303:Rats, Inbred Dahl; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D019422:Dietary Sucrose; D004095:Dihydropyridines; D017311:Amlodipine; C065927:cilnidipine