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 ¼ 18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n ¼ 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 0 -deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (Po0.05) 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.

Reduction in microalbuminuria by calcium channel blockers in patients with type 2 diabetes mellitus and hypertension-A randomized, open-label, active-controlled, superiority, parallel-group clinical trial

“…Cilnidipine dilates both afferent and efferent arterioles and consequently reduces intraglomerular pressure, which is associated with its anti‐proteinuric properties . Cilnidipine reduced urine albumin excretion and 8‐hydroxy‐deoxyguanosine, a marker of oxidative stress, compared with amlodipine treatment . Therefore, the antioxidative properties of cilnidipine have been suggested to be associated with its anti‐proteinuric effect.…”

Serum soluble (pro)renin receptor levels in patients with essential hypertension

“…Hypertensive patients were either untreated or treated only with calcium channel blockers except cilnidipine, which inhibits L-type and N-type calcium channels and could affect the RAS. 13–15 Patients who had suffered from a hemorrhagic stroke or cardiac infarction in the previous 6 months, pregnant women and those with apparent peripheral vascular, malignant disease or uncontrolled diabetes mellitus (hemoglobin A1c (HbA1c) of higher than 10.0%) were excluded. All participants were enrolled after obtaining informed consents approved by the ethical committee of Tokyo Women’s Medical University.…”

Effect of N- and T-type calcium channel blocker on proteinuria, blood pressure and kidney function in hypertensive patients: a meta-analysis

“…In our analysis, as the blood pressure between the two groups was comparable, the reduced proteinuria and preserved kidney function, including eGFR and serum creatinine, might be the result Renal effects of N-and T-type CCB N Thamcharoen et al of the non-hemodynamic effects of the L/N-and L/T-type CCBs, including antioxidant effects. 24,30,55 On the other hand, the antiproteinuric effects of L/N-and L/T-type CCBs could also be explained by their ability to decrease nocturnal and morning blood pressure, especially in patients with CKD who lack the circadian blood pressure rhythm, so called non-dipper-type hypertension. 56 The use of RAAS blockers and diuretics in patients with CKD has previously been shown to lower nocturnal blood pressure in the subset of non-dipper hypertensives, hence reducing in proteinuria.…”