Effects Of Cilnidipine Research Articles

Effects of L-/N-Type Calcium Channel Blockers on Angiotensin II-Renin Feedback in Hypertensive Patients.

Objectives Cilnidipine, an L-/N-type calcium channel blocker (CCB), has unique organ-protective properties due to suppression of hyperactivity in the sympathetic nervous system and renin-angiotensin system (RAS). In this study, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing the RAS. Methods A total of 25 hypertensive patients receiving a RAS inhibitor were randomly assigned to a cilnidipine (n = 12) or amlodipine (n = 13) group. The effects of cilnidipine on proteinuria and angiotensin II–renin feedback were assessed. Results After 6 months of treatment, both systolic and diastolic blood pressures were significantly reduced to a similar extent in both groups. The urine albumin-to-creatinine ratio was significantly lower in the cilnidipine group (p < 0.05) than in the amlodipine group. Amlodipine increased plasma angiotensin I and angiotensin II levels (p < 0.05), whereas cilnidipine did not. Interestingly, the cilnidipine group had a higher ratio of angiotensin-(1–7) (Ang-(1–7)) to angiotensin II in plasma than the amlodipine group (p < 0.05). Conclusions The L-/N-type CCB cilnidipine, but not amlodipine, decreased urinary albumin excretion in hypertensive patients. Cilnidipine also increased the ratio of Ang-(1–7) to angiotensin II in plasma, which might be one factor underlying its beneficial effects.

Effect of L/N-type Calcium Channel Blocker (Cilnidipine) on Oxidative Stress in Nitric Oxide-Deficient Hypertensive Rats

Background: The sympathetic nervous system plays a major role in the renal function through the vasoactive system and the Renin-Angiotensin-Aldosterone System. Even though interest in the renal protective effects of sympathetic blocker has been increased, there are not much data to clarify this efficiency in nitric oxide deficient hypertensive rats. Aim and Objectives: To find out the effect of cilnidipine, L/N-type calcium channel blocker on oxidative stress of kidney in nitric oxide synthase (NOS) inhibited experimental hypertensive rats. Material and Methods: Male Albino Wistar rats (n-24) were randomly allocated into four groups: group 1, control received vehicle; group 2, received Cilnidipine; group 3, received NG-nitro-L-arginine methyl ester hydrochloride (L-NAME); group 4, received L-NAME C All drugs are given orally for 4 weeks. Blood pressure was measured before and after the intervention and twice during intervention for all the rats. On the 29th day, blood was collected and animals were sacrificed and kidneys were collected. Serum and kidney tissue malondialdehyde (MDA) levels are estimated. Results: The results demonstrate that there is a significant increase in Mean Arterial Pressure (MAP) in L-NAME treated rats compared to the control group. Treatment with cilnidipine significantly decreases the MAP in group 4 rats. We also demonstrated the significantly elevated serum and kidney tissue MDA levels in L-NAME treated rat. Treatment with Cilnidipine reduced serum and kidney tissue MDA levels in group 4 rats compared to group 3 rats. Conclusion: The results demonstrate that cilnidipine has suppressive effects against progressive renal injury as evidenced by decreased oxidative stress indicator MDA levels in NO deficient hypertensive rats. This effect is explained by the L/N type calcium channel inhibition of cilnidipine, the L-type calcium channel blocking action lowers blood pressure and N-type calcium channel blocking action leads to suppression of the sympathetic nerve activity and renin-angiotensin-aldosterone system.

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Effects of Cilnidipine, an L/N-Type Calcium Channel Blocker, on Carotid Atherosclerosis in Japanese Post-Stroke Hypertensive Patients: Results from the CA-ATTEND Study.

Aims: Although several antihypertensive agents reduced the carotid intima-media thickness (IMT), it remains unclear whether those agents affect the interadventitial diameter (IAD). We aimed to examine whether cilnidipine, an L/N-type calcium channel blocker, reduced the common carotid IMT or IAD in post-stroke hypertensive patients.Methods: The common carotid IMT and IAD were measured at the start of cilnidipine treatment and 12 months from that. The changes in the mean max-IMT or IAD between baseline and the 12-month follow-up were evaluated and compared between the thick group (max-IMT ≥ 1.1 mm) and the normal group (max-IMT < 1.1 mm).Results: A total of 603 post-stroke hypertensive subjects (mean age = 69.3 yr, 378 males) were included in the analysis. At baseline, IAD was increased stepwise according to the value of max-IMT (p for trend < 0.001). Among them, 326 subjects were followed up for 12 months. The mean max-IMT from baseline to 12 months did not change in the normal group (−0.01 mm, 95% confidence interval [CI] −0.03 to 0.01, n = 170), whereas a significant reduction was observed in the thick group (−0.09 mm, 95% CI −0.13 to −0.05, n = 156). The mean IAD was significantly reduced during the study period in the normal group (−0.14 mm, 95% CI −0.22 to −0.05) as well as in the thick group (−0.12 mm, 95% CI −0.21 to −0.03).Conclusions: Cilnidipine promoted the regression of common carotid IMT in post-stroke hypertensive patients, especially in the thick group. Cilnidipine also reduced the IAD in both normal and thick groups.

Comparative assessment of effects of calcium channel antagonists, amlodipine, and cilnidipine, on QT interval in hypertensive patients - An observational study

Background: The duration of the QT interval as measured by 12-lead electrocardiography is a measure of myocardial repolarization and is widely used to describe cardiac abnormalities, to determine the presence of cardiac toxicity and to evaluate drug safety. In hypertension, the QT interval is a predictor of the risk of both coronary events and cardiovascular death, after adjusting for the effects of additional risk factors. According to AHA and JNC VIII calcium channel blockers are first-line drug in the treatment of hypertension. The equipotent antihypertensive effect of cilnidipine and amlodipine in their equivalent dose has been demonstrated in number of studies. Aims and Objectives: To compare and evaluate the effects of calcium channel antagonists amlodipine and cilnidipine on QT interval among hypertensive patients. Materials and Methods: A total of 258 patients were screened, examined, and enrolled as study participants during that period. The enrolled patients were then divided as (1) hypertensive patient (n = 159) - selected patients received either amlodipine (2.5–10 mg) or cilnidipine (5–20 mg) with or without angiotensin receptor blocker (ARB) and (2) hypertensive with controlled diabetic patients (n = 99) - selected patients received either amlodipine (2.5–10 mg) or cilnidipine (5–20 mg) with or without ARB along with antidiabetic medication. Calculated by Bazett’s formula (most commonly used) = QT Interval/√ (relative risk [RR] interval) where RR interval = 60/heart rate, normal QTc ≤440 ms. The QT interval was measured at the baseline and after 12 months of treatment for hypertensive patients. Results: There was extremely significant QTc reduction was seen with cilnidipine therapy and significant elevation seen by amlodipine treatment but without any clinical relevance. While comparing the effect of amlodipine and cilnidipine, extremely significant as well as clinically relevant difference between the two treatments was noted. Conclusions: From this study, it can be concluded that cilnidipine reduces QTc interval, and hence is a better choice over amlodipine for patients suffering from long QT interval.

Comparison of the effects of L-type calcium channel antagonist Amlodipine with L/N-type calcium channel antagonist Cilnidipine on blood pressure, heart rate, proteinuria and lipid profile in hypertensive patients

Background: Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity.Objective and methods: The purpose of this study was to assess the effect of Cilnidipine and Amlodipine on blood pressure (BP) levels. We did BP monitoring before and after once-daily use of Cilnidipine and Amlodipine in 100 hypertensive patients.Results: Both drugs significantly reduced systolic BP (SBP) and diastolic BP (DBP). However, the reductions in pulse rate (PR) were significantly greater in the Cilnidipine group than the Amlodipine group. N-type calcium channel blockade by Cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.Conclusion: There was significant reduction in proteinuria with Clindipine as compared to Amlodipine. However, there were no significant change in total cholesterol level in diabetes and non-diabetics in both the group.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.460-465

Effects of cilnidipine on systolic and diastolic blood pressure and arteriosclerosis in uncontrolled hypertension with diabetes and sleep apnea syndrome

Effects of cilnidipine on systolic and diastolic blood pressure and arteriosclerosis in uncontrolled hypertension with diabetes and sleep apnea syndrome

Effects of Cilnidipine on Heart Rate and Uric Acid Metabolism in Patients With Essential Hypertension.

BackgroundThe relation between hypertension and hyperuricemia has been established by epidemiological studies. Calcium channel blockers are one of the first-line drugs for newly diagnosed patients with essential hypertension. Cilnidipine is a new calcium channel blocker acting by blocking both L- and N-type calcium channels. The aim of this study was to compare the effectiveness of amlodipine and cilnidipine in patients with essential hypertension and their effects on heart rate and serum uric acid levels.MethodsOut of 100 enrolled patients, 92 completed the study. They were randomly assigned to amlodipine (N = 47) and cilnidipine (N = 45) groups. Cilnidipine was started at 10 mg/day and then adjusted to 5 - 20 mg/day, and amlodipine was started at 5 mg/day and then adjusted to 2.5 - 10 mg/day.ResultsAfter 24 weeks of study, patients in cilnidipine groups showed significant reduction in heart rate and serum uric acid levels from baseline (P = 0.00).ConclusionIn clinical setting where both hypertension and hyperuricemia exist, cilnidipine can be a promising drug of choice.

Effects of cilnidipine and L-type calcium channel blockers on renal functions in hypertensive patients: a meta-analysis of the randomized trials

Effects of cilnidipine and L-type calcium channel blockers on renal functions in hypertensive patients: a meta-analysis of the randomized trials

Effect of cilnidipine on blood pressure, heart rate and proteinuria in comparison with amlodipine

Effect of cilnidipine on blood pressure, heart rate and proteinuria in comparison with amlodipine

Renoprotective and antioxidant renal effects of cilnidipine in DOCA Salt -Treated Albino Rats

Aim: Cilnidipine is a dihydropyridine calcium channel blocker (CCB) that blocks both L-type and N- type channels at the smooth muscle in the artery and calcium channels at the presynaptic nerve terminal, respectively. It is dihydropyridine calcium antagonist that possesses a slow-onset, long-lasting vasodilating effect. The present study is designed to determine the effect of cilnidipine on creatinine clearance, thiobarbituric acid reactive substance, as an index of lipid peroxidation. Additionally, the level of superoxide dismutase enzyme in erythrocyte lysates and kidney catalase enzyme activitiy will be measured. Thirty-six albino rats are divided into 3 separate groups: rats of group 1 are control group, rats of group 2 are administered by deoxycorticosterone acetate (DOCA) salt sc twice/week + 1% NaCl for 2 weeks to be rendered hypertensive) and group 3 will receive 9 mg/kg cilnidipine for 3 weeks intragastrically after induction of hypertension by DOCA-salt as group 2. Results: DOCA-injected albino rats show marked reduction in creatinine clearance. Treatment with cilnidipine improves creatinine clearance compared to the non-treated hypertensive group 2. Additionally, it reduces thiobarbituric acid reactive substance, as an index of lipid peroxidation, with a significant increase in superoxide dismutase enzyme in erythrocyte lysates and kidney catalase enzyme activities. Conclusion: This study points to the possible beneficial renal protective effects of cilnidipine in hypertensive albino rats injected with DOCA for 2 weeks.

Effects of cilnidipine on sympathetic outflow and sympathetic arterial pressure and heart rate regulations in rats

AimsCilnidipine is a unique Ca2+ channel blocker that inhibits both L-type and N-type Ca2+ channels. The present study aimed to assess the effects of intravenous cilnidipine on sympathetic outflow and sympathetic arterial pressure (AP) and heart rate (HR) regulations. Main methodsCarotid sinus baroreceptor regions were isolated from the systemic circulation in anesthetized and vagotomized Wistar Kyoto rats. Changes in efferent sympathetic nerve activity (SNA), AP and HR in response to a stepwise input of carotid sinus pressure were examined before and during intravenous cilnidipine administration (30μg/kg bolus+100μgkg−1h−1 infusion, n=6). Key findingsCilnidipine significantly reduced the AP response range (from 68.0±10.2 to 34.6±4.1mmHg, P=0.007) but did not affect the SNA response range (from 90.4±10.3 to 84.7±9.5%, P=0.297) or the HR response range (from 50.4±10.1 to 48.1±6.2beats/min, P=0.719). SignificanceCilnidipine, at a depressor dose used in the present study, does not acutely suppress sympathetic outflow from the central nervous system. Also, it spared the sympathetic HR response, suggesting that N-type Ca2+ channel blocking action at the cardiac sympathetic nerve endings may be a modest one.

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

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.

Cilnidipine regulates glucose metabolism and levels of high-molecular adiponectin in diet-induced obese mice

The aim of the present study is to examine the effects of the antihypertensive drug cilnidipine on glucose metabolism and adipocytokines, including adiponectin, in diet-induced obese (DIO) mice. The effects of cilnidipine on insulin sensitivity and the levels of adiponectin in DIO mice were examined after the mice had been treated with cilnidipine dissolved in water at a dose of 0.2 g l(-1) for 14 days. As expected, treatment with cilnidipine decreased the systolic and diastolic blood pressures in DIO mice, compared with control mice (P<0.05 for each parameter). Cilnidipine treatment improved glucose and insulin sensitivity in DIO mice. In addition, cilnidipine treatment dramatically increased the level of adiponectin in white adipose tissue (P<0.05) and the circulating levels of total and high-molecular weight (HMW) adiponectin in DIO mice (P<0.01 for each parameter). Furthermore, the secretion of HMW adiponectin and the ratio of HMW adiponectin/total adiponectin were both increased after cilnidipine treatment. Finally, the secretion of adiponectin from adipocytes was increased after cilnidipine treatment. Taken together, these results indicate that cilnidipine improves insulin tolerance and adiponectin levels, especially high-molecular type adiponectin, in DIO mice.

Role of the phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways in the neuroprotective effects of cilnidipine against hypoxia in a primary culture of cortical neurons

Cilnidipine, a calcium channel blocker, has been reported to have neuroprotective effects. We investigated whether cilnidipine could protect neurons from hypoxia and explored the role of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal-related kinase (ERK) pathways in the neuroprotective effect of cilnidipine. The viability of a primary culture of cortical neurons injured by hypoxia, measured by trypan blue staining and lactate dehydrogenase (LDH) assay, was dramatically restored by cilnidipine treatment. TUNEL and DAPI staining showed that cilnidipine significantly reduced apoptotic cell death induced by hypoxia. Free radical stress and calcium influx induced by hypoxia were markedly decreased by treatment with cilnidipine. Survival signaling proteins associated with the PI3K and ERK pathways were significantly increased while death signaling proteins were markedly decreased in the primary culture of cortical neurons simultaneously exposed to cilnidipine and hypoxia when compared with the neurons exposed only to hypoxia. These neuroprotective effects of cilnidipine were blocked by treatment with a PI3K inhibitor or an ERK inhibitor. These results show that cilnidipine protects primary cultured cortical neurons from hypoxia by reducing free radical stress, calcium influx, and death-related signaling proteins and by increasing survival-related proteins associated with the PI3K and ERK pathways, and that activation of those pathways plays an important role in the neuroprotective effects of cilnidipine against hypoxia. These findings suggest that cilnidipine has neuroprotective effects against hypoxia through various mechanisms, as well as a blood pressure-lowering effect, which might help to prevent ischemic stroke and reduce neuronal injury caused by ischemic stroke.

Additive effects of cilnidipine and angiotensin II receptor blocker in preventing the progression of diabetic nephropathy in diabetic spontaneously hypertensive rats

Cilnidipine (Cil) is an L/N-type calcium channel blocker (CCB) that is known to provide renal protection by decreasing the activity of the sympathetic nervous system and the renin-angiotensin system (RAS). However, very few studies have evaluated the renoprotective effects of Cil in hypertension complicated by diabetes mellitus. In this study, we compared the effects of cilnidipine and the L-type CCB, amlodipine (Aml), in combination with an angiotensin II receptor blocker (ARB) on diabetic nephropathy that developed as a result of inducing diabetes in hypertensive rats. Diabetes was induced in 9-week-old male spontaneously hypertensive rats by intraperitoneally injecting them with streptozotocin (40 mg/kg twice) and the rats (8 per group) were randomly assigned to receive valsartan (Val), Cil + Val, Aml + Val, or vehicle for 8 weeks through a gastric tube. There were no significant differences in systolic blood pressure or plasma parameters between the two combination therapy groups. Blood pressure lowering by neither combination therapy significantly affected the glycemic variables. However, the increased glycogen levels in the kidney as a result of hyperglycemia were significantly suppressed in the groups that received combination therapy, and the increased proteinurea and glomerulosclerosis due to progression of the diabetic nephropathy were significantly suppressed in the Cil + Val group. In addition, a significant decrease in ED-1-positive cells was observed in the Cil + Val group alone. The results of this study suggested that the L/N-type CCB, cilnidipine, had additive antihypertensive and proteinuria-lowering effects when administered in combination with an ARB, even in type-1 diabetic rats, and that the L-type CCB, amlodipine, did not. Furthermore, combination therapy with cilnidipine and valsartan significantly reduced glycogen accumulation and ED-1-positive cell infiltration, suggesting that cilnidipine suppressed the excessive increase in the activity of the sympathetic nervous system and RAS through N-type calcium channel blockade.

Effects of Cilnidipine on Serum Uric Acid Level and Urinary Nitrogen Monoxide Excretion in Patients with Hypertension

The effects of cilnidipine on the serum uric acid level and urinary NO excretion in hypertensive patients were investigated. Blood and urine samples of 16 hypertensive outpatients were collected before and 2 months after cilnidipine therapy (10 mg). The serum uric acid level decreased significantly after cilnidipine treatment, while the uric acid–creatinine clearance ratio was unaffected. The cilnidipine medication produced a significant increase in urinary NO excretion, although amlodipine did not change it significantly. Therefore, cilnidipine has a profound antihypertensive effect and may reduce the serum uric acid level and increase NO production in the kidney.

Cilnidipine Lowers Plasma Leptin of Patients with Obese Hypertension Associated with Cerebrovascular Disorder

Background: Since cilnidipine suppresses not only the L-type but also N-type calcium channels found on peripheral sympathetic nerve endings which control noradrenaline release, it is thought to be a Ca antagonist with low sympathetic nerve activation when lowering blood pressure (dual blocking action). As activation of sympathetic nervous system is suggested to contribute to hypertension in obesity, dual blocking action of cilnidipine may contribute to patients with obesity-hypertension. Methods: The effects of cilnidipine on plasma leptin levels and blood pressure were studied. Twenty three patients with obesity-hypertension associated with a past history of stroke or ischemic changes confirmed by brain magnetic resonance imaging were enrolled. Cilnidipine (10 mg/day) was administered orally once a day after breakfast. The duration of the study treatment was 12 weeks. Retroperitoneal adipose tissues around the kidney of both fat and lean cadaver and neuronal and non-neuronal tissues of rat were used for immunohistochemical examination. Result: The mean circulating leptin level decreased from 11.8 ng/ml to 10.8 ng/ml that reached statistical significance. Multiple regression analysis revealed no significant effects of covariates except for baseline leptin level. An immunohistochemical study revealed that N-type calcium channel protein was expressed on the cell membrane of adipocytes. We speculate that a blockade of calcium current through the N-type channel, instead of the L-type channel may suppress leptin secretion. Conclusion: The dual blocking action of cilnidipine may help control both arterial hypertension and leptininduced atherosclerosis in patients with obese hypertension associated with cerebrovascular disorder.

Renoprotective Effect of the L/N-Type Calcium Channel Antagonist Cilnidipine on Puromycin Aminonucleoside-Induced Nephrosis in Rats

The renoprotective effect of cilnidipine ((+/-)-2-methoxyethyl 3-phenyl-2(E)-propenyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate, CAS 132203-70-4), a L/N-type calcium channel antagonist, on puromycin aminonucleoside (PAN)-induced nephrosis was investigated in rats. In the Experiment I, rats were given an intravenous injection of PAN (70 mg/kg). Cilnidipine (3 mg/kg/day) and enalapril (CAS 75847-73-3, 5 mg/kg/day) were administered orally from 6 days after treatment with PAN (day 6) to day 26, and urinary analysis was performed on days 9, 15, 20 and 27. In the Experiment II, nephrosis was also induced by intravenous injection of PAN (70 or 100 mg/kg) in rats which were treated with cilnidipine and enalapril from days 6 to 10. Systolic blood pressure was measured on day 7 and urinary analysis was performed on day 10. On day 11, serum was collected and the kidneys were removed for immunofluorescence staining for nephrin and podocin proteins. In PAN-treated rats, the daily urinary protein excretion was dramatically elevated on day 5, reached a peak on day 9 and gradually returned to a normal level from days 15 to 27. Cilnidipine (3 mg/kg/ day) significantly suppressed the increase in proteinuria on day 9 and also improved the decrease in creatinine clearance without evident effect on the blood pressure. Furthermore, the elevations in serum total cholesterol and triglyceride tended to be suppressed by cilnidipine. The expression of nephrin and podocin proteins in PAN-treated rats showed the granular pattern in the glomeruli, while the intensity of staining seemed to be dependent on the urinary protein excretion level in the cilnidipine-treated rats. The results obtained in this study suggest a renoprotective effect of cilnidipine in PAN-induced nephrosis in rats.

Abstract P160: N-Type Ca 2+ Channel Blockade Prevents Sudden Death in Mice with Heart Failure

Background - Increased sympathetic nerve activity is involved in the increased arrhythmogenicity seen in patients with chronic heart failure. N-type Ca 2+ channel (NCC) modulates sympathetic nerve activity by regulating calcium entry at sympathetic nerve terminal, which triggers the release of the neurotransmitter noradrenalin. The ability of NCC blockade to prevent lethal arrhythmias associated with heart failure has never been tested, however. Methods and Results - We compared effects of cilnidipine (Cil), dual N-and L-type Ca 2+ channel blocker, with those of nitrendipine (Nit), a selective L-type Ca 2+ channel blocker, in a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor transgenic mice (dnNRSF-Tg), a mouse model of dilated cardiomyopathy leading to sudden arrhythmic death. Hemodynamic and echocardiographic analyses showed no significant difference among the control, Cil, and Nit groups. In contrast, Cil dramatically improved the survival rate (p&lt;0.001) and reduced ventricular arrhythmia (p&lt;0.05) among dnNRSF-Tg mice, compared with control vehicle or Nit (n=22 for WT, n=20 for Tg without drugs, n=22 for Tg with Cil, n=23 for Tg with Nit). Cil improved the imbalance in autonomic nerve activity assessed by heart rate valiability, and also reduced the increased urinary excretion of noradrenalin seen in dnNRSF-Tg, whereas Nit did not. Conclusions - NCC blockade ameliorated disturbed autonomic nerve function and improved survival in a mouse model of dilated cardiomyopathy and sudden death. Our findings suggest NCC blockade is a potentially useful approach to preventing sudden cardiac death in patients with heart failure.