Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injuries in Dahl salt-sensitive rats.
The sympathetic nerve activity plays an important role on the renal function through the vasoactive system and the renin-angiotensin system. Although interest in the renal protective effects of anti-sympathetic agents has been increased, there are not enough data to clarify this efficiency. Therefore, we investigated the effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injury in Dahl salt-sensitive (Dahl S) rats. Male Dahl S rats (6 weeks of age) were fed a high salt (4% NaCl) diet. They were divided into groups with similar blood pressure at 12 weeks of age and they received vehicle (n=7) or cilnidipine (30 mg/kg/d as food admix, n=9) for 8 weeks. Cilnidipine treatment suppressed the increase in systolic blood pressure. Although urinary protein excretion was not influenced, cilnidipine inhibited the increase in blood urea nitrogen and decrease in creatinine clearance. Histological investigation revealed that progression of glomerular sclerosis was inhibited in cilnidipine treatment group. Of notes, cilnidipine reduced plasma norepinephrine level and plasma rennin activity compared with vehicle-treated Dahl S rats. These data indicated that cilnidipine has suppressive effects against progressive renal injury in Dahl S rats. This effect is not only explained by the L-type calcium channel blocking action that lowered blood pressure, but also partially explained by the N-type calcium channel blocking action that lead to suppression of the sympathetic nerve activity and renin-angiotensin system.
Konda
Tomoyuki
T
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Kanagawa, Japan. tomoyuki_konda@ajinimoto.com
Enomoto
Azusa
A
Takahara
Akira
A
Yamamoto
Hiroshi
H
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D004095:Dihydropyridines / Q000627:therapeutic use*; D018450:Disease Progression; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012083:Renin / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D014841:von Willebrand Factor; D000804:Angiotensin II; C065927:cilnidipine; D012083:Renin; D009638:Norepinephrine