Cilnidipine, an N/
L-type calcium channel blocker, has been reported to inhibit sympathetic nerve activity and has a greater renoprotective effect than
L-type calcium channel blockers. To investigate the hypothesis that
cilnidipine might ameliorate advanced
hypertensive nephropathy and inhibit the renal renin-angiotensin-aldosterone system,
cilnidipine (1 mg per kg per day) or
amlodipine (1 mg per kg per day) was administered to uninephrectomized
deoxycorticosterone (
DOCA)-
salt hypertensive rats (
DOCA-
salt) for 4 weeks by gavage. Although the blood pressure in the
DOCA-
salt group was higher than that of control, neither
cilnidipine nor
amlodipine had any effect on the increase in blood pressure in the
DOCA-
salt group. The
DOCA (40 mg per kg per week, subcutaneously (s.c.)) and
salt (1% NaCl in
drinking water) treatment significantly aggravated the levels of urinary
protein excretion and
creatinine clearance and increased glomerulosclerosis and
collagen deposition in the tubulointerstitial area of the kidney. These effects were attenuated by
cilnidipine treatment. Reverse transcription-polymerase chain reaction analysis revealed that the renal expression of
mRNA for
collagen I/IV and
transforming growth factor-β was enhanced in the
DOCA-
salt group and that the overexpression of these molecules was suppressed by
cilnidipine.
Nicotinamide adenine dinucleotide phosphate (
NADPH) oxidase-derived
superoxide production in the kidney and urinary
norepinephrine excretion, which were enhanced in the
DOCA-
salt group, were suppressed by
cilnidipine.
Cilnidipine also decreased the activity and expression of
angiotensin-converting enzyme (ACE) and the
aldosterone concentration in the renal homogenate. Although neither
cilnidipine nor
amlodipine had any effect on the increased blood pressure in the
DOCA-
salt group, these renal changes were not induced by treatment with
amlodipine. In conclusion,
cilnidipine inhibited renal dysfunction, sympathetic nerve activity and renal renin-angiotensin-aldosterone system in the
DOCA-
salt group.