The L/N-Type Calcium Channel Blocker, Cilnidipine, Reduces Heart Rate and Albuminuria in Patients with Type 2 Diabetes

Tanaka, Masami

doi:10.1177/147323001003800222

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…In agreement with the findings of previous animal and clinical studies (4, 30, 31), cilnidipine, an N/L-type CCB, demonstrated strong anti-proteinuric and anti- albuminuric effects in HS-UNX-SHR, confirming its reno-protective effects in hypertensive renal damage. Results from the renal Ang II and glomerular desmin staining experiments also suggest that cilnidipine inhibits renal RAS and protects podocytes.…”

Section: Discussionsupporting

confidence: 91%

N-type Calcium Channel Inhibition With Cilnidipine Elicits Glomerular Podocyte Protection Independent of Sympathetic Nerve Inhibition

et al. 2012

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We recently demonstrated that cilnidipine, an L/N-type calcium channel blocker, elicits protective effects against glomerular podocyte injury, in particular, in obese hypertensive rats that express the N-type calcium channel (N-CC). Since the N-CC is known to be expressed in sympathetic nerve endings, we evaluated the reno-protective effects of cilnidipine in innervated and denervated spontaneously hypertensive rats (SHR). Male SHR were uninephrectomized and fed 4% high-salt diet (HS-UNX-SHR). Animals were divided into groups, as follows, and observed from 9 to 27 weeks of age: 1) vehicle (n = 14), 2) vehicle plus renal-denervation (n = 15), 3) cilnidipine (50 mg/kg per day, p.o.; n = 10), and 4) cilnidipine plus renal-denervation (n = 15). Renal denervation attenuated elevations in blood pressure, but failed to suppress urinary protein excretion and podocyte injury in HS-UNX-SHR. Cilnidipine in both innervated and denervated HS-UNX-SHR similarly induced significant antihypertensive effects, as well as suppressing the urinary protein excretion and podocyte injury, compared to vehicle-treated HS-UNX-SHR. These data indicate that renal nerves have a limited contribution to the cilnidipine-induced reno-protective effects in HS-UNX-SHR.

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Section: Discussionsupporting

confidence: 91%

N-type Calcium Channel Inhibition With Cilnidipine Elicits Glomerular Podocyte Protection Independent of Sympathetic Nerve Inhibition

et al. 2012

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“…Our study also showed a statistically significant difference in the change in mean UPCR values from baseline to 12 weeks between the amlodipine and cilnidipine groups, which is in concordance with studies done by Zaman ZA et al, 18 Abe M et al, 38 Uchida S et al, 44 Fujita T et al 40 and Kojima S et al 39 A significant decrease in albumin-creatinine ratio among hypertensive patients with type 2 diabetes mellitus was observed in a study done by Tanaka M et al, 31 which showed a positive correlation with the change in heart rate indicating cilnidipine may exert its renoprotective effect by inhibiting sympathetic nervous activity. The anti-proteinuric action of cilnidipine can also be attributed to its action on N-type calcium channels present in the kidneys.…”

Section: Effect On Proteinuriasupporting

confidence: 85%

“…No significant difference was observed between either genders and also between diabetic and non-diabetic patients. A similar statistically significant decrease in heart rate has been observed with cilnidipine therapy in a study done by Manthri S et al 30 A study by Tanaka M et al 31 has shown a significant decrease in heart rate with cilnidipine therapy in 25 hypertensive subjects also having type 2 diabetes mellitus. Also, a significant decrease in heart rate with cilnidipine therapy has been observed in hypertensive patients with CKD on treatment with an RAS inhibitor in a study done by Hatta T et al 32 Our study also showed a significant difference in the change in mean heart rate from baseline at 6 weeks and 12 weeks between the amlodipine and cilnidipine groups.…”

Section: Effect On Heart Ratesupporting

confidence: 66%

A Study of the Effects of Amlodipine and Cilnidipine on Haemodynamic Parameters and Renoprotection in Hypertensive Subjects With Proteinuria

Gowda¹,

Ramesh²

2017

jemds

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BACKGROUND Hypertension with chronic kidney disease is a widely prevalent public health concern. Calcium channel blockers are a commonly used class of drugs for the treatment of hypertension. L-type calcium channel blockers like amlodipine cause a reflex sympathetic overactivity, which predisposes to increased cardiovascular morbidity and mortality. Also, the effect of L-type CCBs on urinary protein excretion is uncertain. Cilnidipine is a novel CCB with a dual L/N-type calcium channel blocking property, thus favouring additional renal and cardiovascular protection. The objective of this study is to evaluate the effects and their linearity across the timeframe of amlodipine and cilnidipine in hypertensive subjects with proteinuria on heart rate, blood pressure, lipid profile and proteinuria. MATERIALS AND METHODS After Institutional Ethical Committee approval, a prospective, randomised and open-label study was carried out on hypertensive subjects with proteinuria attending the General Medicine OPD in K. R. Hospital, Mysore. Sixty subjects satisfying the inclusion and exclusion criteria were included in the study. Heart rate, blood pressure, lipid profile (TC, LDL, HDL, TG) and Urine Protein-to-Creatinine Ratio (UPCR) were measured at baseline. Blood pressure and heart rate were monitored at weekly intervals until the end of 12 weeks. While lipid profile was reassessed at 6 weeks and 12 weeks, UPCR was reassessed at the end of 12 weeks. Descriptive statistics, independent sample 't' test, repeated measure ANOVA and Cramer's V test were used to analyse the results. RESULTS Demographic profile was well matched in both the groups. In the Amlodipine group, the heart rate was significantly higher tha n that before treatment, whereas subjects in the cilnidipine group had a significantly lower heart rate when compared to baseline (p < 0.05). There was no significant difference in mean SBP and mean DBP values, either within each group or between the two groups. Also, the UPCR was significantly decreased in the cilnidipine group as opposed to the amlodipine group where it wa s significantly increased, thereby resulting in a significant intergroup difference (p < 0.05). However, neither of the drugs caused a significant change in the lipid parameters and the intergroup difference was also statistically insignificant. CONCLUSION Cilnidipine is thus, a better alternative in hypertensive patients with proteinuria due to its cardioprotective and renoprotective actions.

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“…In addition, ivabradine, a selective PR‐lowering drug, has been reported to reduce cardiovascular mortality or hospitalization of patients with heart failure 31 . The PR‐lowering effect of cilnidipine has been confirmed by several reports, 18,19,32 although that of amlodipine is controversial, 15–17 significant PR reduction was not observed in the open‐label repeated studies in patients treated with L‐type Ca channel blockers, amlodipine, 33 lercanidipine, and nifedipine GITS 34 . Cilnidipine lowered MPR only in the high MPR group.…”

Section: Discussionmentioning

confidence: 94%

The Effects of the L / N‐Type Calcium Channel Blocker (Cilnidipine) on Sympathetic Hyperactive Morning Hypertension: Results From ACHIEVE‐ONE*

Kario¹,

Ando²,

Kido³

et al. 2012

J of Clinical Hypertension

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The Ambulatory Blood Pressure Control and Home Blood Pressure (Morning and Evening) Lowering By N‐Channel Blocker Cilnidipine (ACHIEVE‐ONE) trial is a large‐scale clinical study on blood pressure (BP) and pulse rate (PR) in the real world with use of cilnidipine, a unique L/N‐type Ca channel blocker, possessing a suppressive action on increased sympathetic activity in patients with essential hypertension. The effects of cilnidipine on morning hypertension were examined. The authors examined 2319 patients treated with cilnidipine for 12 weeks. Clinic systolic BP (SBP) decreased by 19.6 mm Hg from 155.0 mm Hg, whereas morning SBP decreased by 17.0 mm Hg from 152.9 mm Hg after 12‐week cilnidipine treatment. Cilnidipine reduced both morning SBP and PR more markedly in patients with higher baseline morning SBP (−3.2 mm Hg and −1.3 beats per minute in the first quartile of morning SBP, −30.9 mm Hg and −3.2 beats per minute in the fourth quartile), and also reduced both morning PR and SBP more markedly in patients with higher baseline morning PR (0.6 beats per minute and −15.6 mm Hg in <70 beats per minute, and −9.7 beats per minute and −20.2 mm Hg in ≥85 beats per minute). Cilnidipine significantly reduced BP and PR in hypertensive patients at the clinic and at home, especially with higher BP and PR in the morning. J Clin Hypertens (Greenwich). 2012; 00:00–00. ©2012 Wiley Periodicals, Inc.

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The L/N-Type Calcium Channel Blocker, Cilnidipine, Reduces Heart Rate and Albuminuria in Patients with Type 2 Diabetes

Cited by 12 publications

References 30 publications

N-type Calcium Channel Inhibition With Cilnidipine Elicits Glomerular Podocyte Protection Independent of Sympathetic Nerve Inhibition

N-type Calcium Channel Inhibition With Cilnidipine Elicits Glomerular Podocyte Protection Independent of Sympathetic Nerve Inhibition

A Study of the Effects of Amlodipine and Cilnidipine on Haemodynamic Parameters and Renoprotection in Hypertensive Subjects With Proteinuria

The Effects of the L / N‐Type Calcium Channel Blocker (Cilnidipine) on Sympathetic Hyperactive Morning Hypertension: Results From ACHIEVE‐ONE*

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