Renoprotective and antioxidant effects of cilnidipine in hypertensive patients.

Abstract

Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n=18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n=17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2'-deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (P<0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.

• Authors: Takeshi Soeki, Mitsuhiro Kitani, Kenya Kusunose, Shusuke Yagi, Yoshio Taketani, Kunihiko Koshiba, Tetsuzo Wakatsuki, Shunsuke Orino, Kazuhiro Kawano, Masataka Sata
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 35 Issue 11 Pg. 1058-62 (Nov 2012) ISSN: 1348-4214 [Electronic] England
• PMID: 22763473 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Antioxidants
• Calcium Channel Blockers
• Dihydropyridines
• FABP1 protein, human
• Fatty Acid-Binding Proteins
• Amlodipine
• 8-Hydroxy-2'-Deoxyguanosine
• cilnidipine
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Aged
• Albuminuria (epidemiology)
• Amlodipine (pharmacology, therapeutic use)
• Antihypertensive Agents (pharmacology, therapeutic use)
• Antioxidants (metabolism)
• Blood Pressure (drug effects, physiology)
• Calcium Channel Blockers (pharmacology, therapeutic use)
• Deoxyguanosine (analogs & derivatives, urine)
• Dihydropyridines (pharmacology, therapeutic use)
• Fatty Acid-Binding Proteins (urine)
• Female
• Heart Rate (drug effects, physiology)
• Humans
• Hypertension (drug therapy, metabolism)
• Incidence
• Male
• Middle Aged
• Oxidative Stress (drug effects, physiology)
• Prospective Studies
• Renal Insufficiency, Chronic (prevention & control, urine)