Lercanidipine Treatment Research Articles

Investigation of cardioprotective effect of lercanidipine on doxorubicin-induced cardiotoxicity.

Although doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5mg/kg LRD), LRD 1 (DOX + 1mg/kg LRD), and LRD 2 (DOX + 2mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.

Evaluation of drug interaction between cyclosporine and lercanidipine: a descriptive study

ObjectivesCyclosporine is an immunosuppressive drug with a high potential for drug interactions that is frequently used in renal transplant patients. The purpose of this study was to assess the change...

Effect of antihypertensive treatment with lercanidipine on endothelial progenitor cells and inflammation in patients with mild to moderate essential hypertension

Background: It has been demonstrated that circulating endothelial progenitor cells (EPCs) number reflects the endogenous vascular repair ability, with the EPCs pool declining in presence of cardiovascular risk factors. Several drugs, including dihydropyridine calcium channel blockers, have been reported to elicit antioxidant and anti-inflammatory properties, as well as to improve vascular remodeling and dysfunction. However, no data are available about the effects of lercanidipine on EPCs. The aim of the present study was therefore to investigate the effects of short-term treatment with lercanidipine on circulating EPCs, as well as on indices of inflammation and oxidative stress.Patients and methods: Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine 20 mg per day orally. Investigations were performed in basal condition, after appropriate wash out of previous treatments, and after 4 weeks of lercanidipine treatment. Inflammatory and oxidative stress markers were assessed by ELISA technique. Lin-/7AAD-/CD34+/CD133+/VEGFR-2 + and Lin-/7AAD-/CD34+/VEGFR-2 + cells were identified by flow cytometry and considered as EPCs. EPCs cells were expressed as number of cells per million Lin-mononuclear cells.Results: Circulating EPCs were significantly increased after lercanidipine treatment (CD34+/CD133+/VEGFR-2 + cells: 78.3 ± 64.5 vs 46.6 ± 32.8; CD34+/VEGFR-2+: 87996 ± 165116 vs 1026 ± 1559, respectively, p < 0.05). A modest reduction in circulating indices of inflammation was also observed.Conclusions: In conclusion, lercanidipine is able to increase the number of circulating EPCs, possibly through a reduction of low-grade inflammation.

Effect of Lecarnidipine on hypertension and circulation hematopoietic progenitor cells in the elderly

Objective To investigate the effect of Lecarnidipine on hypertension and circulation hematopoietic progenitor cells (HPCs) count in elderly patients. Methods A total of 61 elderly patients with hypertension were selected in Renji Hospital geriatric hypertension clinic from January 2014 to August 2014. Patients were randomly divided into two groups: Lercanidipine treatment group (n=32, Lercanidipine hydrochloride 5-10 mg/day), the control group (n=29, thiazide diuretics and / or beta blockers according to patient's condition). Patients were observed for 12 weeks, and the target blood pressure level was <140/90 mmHg (1 mmHg=0.133 kPa). Blood lipids and glucose levels, liver and kidney function and erythrocyte sedimentation rate (ESR) were determined before and after treatment. The quantity of circulation HPCs (the percentage of CD34+ CD45dim in peripheral blood in 100000 mononuclear cells) was detected by flow cytometry analysis. Results Blood pressure in Lercanidipine treatment group was decreased after the treatment (P 0.05). The number of CD34+ CD45dim cells was increased after 12 weeks of Lecarnidipine treatment 〔(0.022 + 0.003)% vs.(0.034 + 0.028)%, P 0.05). Taking the number of CD34+ CD45dim as the independent variables, the multiple stepwise linear regression analysis showed that the number of CD34+ CD45dim cells was negatively correlated to systolic pressure. Conclusions The number of circulation HPCs is negatively correlated with systolic pressure in the elderly. Lercanidipine can increase the number of circulation HPCs, and does not rely on its antihypertensive effect. Key words: Hypertension; Hematopoietic stem cells; Calcium channel blockers

Calcium antagonist lercanidipine in hypertension

The article presents the results of studies on the effectiveness and safety of a III generation calcium antagonist lercanidipine in the treatment of hypertension. Lercanidipine treatment leads to a marked significant reduction in systolic and diastolic blood pressure without producing a significant effect on heart rate. The drug has organ-protective effect, reduces left ventricular hypertrophy, improves kidney function and has antiproteinuric action. Lercanidipine is well tolerated, less likely to cause peripheral edema compared with other calcium antagonists.

CXCR7 Upregulation Is Required for Early Endothelial Progenitor Cell–Mediated Endothelial Repair in Patients With Hypertension

Dysfunction of early endothelial progenitor cells (EPCs) is responsible for impaired endothelial repair capacity after arterial injury in patients with hypertension. Here, we hypothesized that diminished signaling of CXC chemokine receptor 7 (CXCR7) contributes to the reduced EPC functions, and enhanced CXCR7 expression restores the capacities of EPCs from hypertensive patients. CXCR7 expression of EPCs from hypertensive patients was significantly reduced when compared with that from healthy subjects. Meanwhile, the phosphorylation of p38 mitogen-activated protein kinase, a downstream signaling of CXCR7, was elevated, which increased cleaved caspase-3 level of EPCs. CXCR7 gene transfer augmented CXCR7 expression and decreased the phosphorylation of p38 mitogen-activated protein kinase, which was paralleled to EPC functional upregulation of in vitro adhesion, antiapoptosis activities, and in vivo re-endothelialization capacity in a nude mouse model of carotid artery injury. The enhanced in vitro and in vivo functions of EPCs were markedly inhibited by neutralizing monoclonal antibody against CXCR7, which was blocked by p38 mitogen-activated protein kinase inhibitor SB203580. Downregulation of cleaved caspase-3 level induced by CXCR7 gene transfer or SB203580 pretreatment improved EPC functions. Furthermore, we found that lercanidipine, a dihydropyridine calcium channel antagonist, enhanced CXCR7 expression and facilitated in vitro and in vivo functions of EPCs. Our study demonstrated for the first time that diminished CXCR7 signal at least partially contributes to the reduced in vitro functions and in vivo re-endothelialization capacity of EPCs from hypertensive patients. Upregulation of CXCR7 expression induced by gene transfer or lercanidipine treatment may be a novel therapeutic target for increased endothelial repair capacity in hypertension.

Lercanidipine effect on polymorphonuclear leukocyte-related inflammation and insulin resistance in essential hypertension patients

Inflammation, insulin resistance and oxidative stress (OS), are among the mechanisms that have been implicated in pathogenesis of essential hypertension (EH). Peripheral polymorphonuclear leukocytes (PMNLs) are primed in EH patients, releasing uncontrolled superoxide anion contributing to OS in these patients. PMNL priming correlates with insulin resistance and with PMNL intracellular calcium ([Ca2+]i). Recent studies have attributed to the anti-hypertensive drug lercanidipine, a third generation calcium-channel blocker, and additional anti-ischemic and anti-oxidative characteristics. To evaluate the possible non-traditional effect of two months of lercanidipine treatment on insulin resistance and on PMNL-related inflammation in EH patients. Non-smoking EH patients with untreated mild to moderate high blood pressure (BP) were included. Low-graded inflammation was reflected by WBC and PMNL counts and by PMNL apoptosis. Systemic inflammation was measured by plasma fibrinogen, C-reactive protein (CRP) and albumin levels. Fasting serum insulin levels served as a marker of insulin resistance. Two months of lercanidipine treatment showed significant decrease in BP, WBC and PMNL counts, and also in PMNL apoptosis, CRP and serum insulin levels and significant increase in serum albumin levels. Rates of superoxide release from PMNLs, WBC and PMNL counts and insulin levels positively correlated with mean arterial blood pressure values. We imply that use of lercanidipine can be favored in EH patients due to its combined anti-PMNL priming and anti-inflammatory effects, in addition to its anti-hypertensive characteristics. Key words: Essential hypertension, lercanidipine, low-graded inflammation, primed polymorphonuclear leukocytes, oxidative stress.

Lercanidipine effect on polymorphonuclear leukocyte-related inflammation and insulin resistance in essential hypertension patients.

IntroductionInflammation, insulin resistance, and oxidative stress (OS) are among the mechanisms that have been implicated in the pathogenesis of essential hypertension (EH). Peripheral polymorphonuclear leukocytes (PMNLs) are primed in EH patients, releasing uncontrolled superoxide anions contributing to OS in these patients. PMNL priming correlates with insulin resistance and PMNL intracellular calcium ([Ca2+]i). Recent studies have attributed additional anti-ischemic and antioxidative characteristics to the antihypertensive drug, lercanidipine, a third-generation calcium-channel blocker. The purpose of this study was to evaluate the possible nontraditional effect of 2 months of lercanidipine treatment on insulin resistance and on PMNL-related inflammation in EH patients.MethodsNon-smoking EH patients with untreated mild-to-moderate high blood pressure (BP) were included. Low-grade inflammation was reflected by PMNL apoptosis and by white blood cell (WBC) and PMNL counts. Systemic inflammation was measured by plasma fibrinogen, C-reactive protein (CRP), and transferrin and albumin levels. Fasting serum insulin levels served as a marker of insulin resistance.ResultsTwo months of lercanidipine treatment showed a significant decrease in BP, WBC, and PMNL counts, PMNL apoptosis, CRP, and serum insulin levels, and a significant increase in serum albumin levels. Rates of superoxide release from PMNLs, WBC and PMNL counts, and insulin levels positively correlated with mean arterial BP values.ConclusionThe use of lercanidipine can be favorable in EH patients due to its combined anti-PMNL priming and anti-inflammatory effects, in addition to its antihypertensive characteristics.

Polymorphism of the methylenetetrahydrofolate reductase gene C677T and its influence on the antihypertensive and vascular protective effects of short-term lercanidipine treatment

ObjectiveTo determine whether the antihypertensive and vascular protective effects of short-term treatment with lercanidipine, a calcium channel blocker, are modulated by the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. MethodsIn a self-controlled study, a total of 143 essential hypertensive patients, all permanent residents of Shanghai, were included. All of them were treated orally with lercanidipine at a single daily fixed dosage of 10mg for 28 consecutive days and the genotypes of the MTHFR C677T polymorphism were determined. Blood pressures, ankle-brachial index values (ABI), and pulse wave velocity (PWV) were measured at baseline and on the 29th day. ResultsThe 110 subjects for whom complete genotype and phenotype information were available were used for final data analysis. Patients with the TT genotype showed higher baseline diastolic blood pressure (DBP) than those with the CC and CT genotypes (P=0.018). Within each genotype group, SBP, DBP and PWV showed significant difference between baseline and after treatment (P<0.05). However, ABI showed significant difference between baseline and after treatment only within the CT and TT groups (P<0.05) but not in the CC group (P>0.05). Patients with the TT genotype presented a greater reduction in normalized PWV than those with the CC and CT genotypes (P=0.02). Patients in all genotype groups had statistically similar changes in normalized SBP, DBP and ABI (P>0.05). ConclusionThe MTHFR gene polymorphism C677T might be associated with the vascular protective effects of short-term lercanidipine treatment. However, the MTHFR C677T polymorphism might not affect the antihypertensive effects of the lercanidipine treatment.

POSITIONS OF CALCIUM CHANNEL BLOCKER LERCANIDIPINE ACCORDING TO EVIDENCE BASED CARDIOLOGY

Data of evidence based cardiology including results of international clinical trials on efficacy and safety of the modern calcium channel blocker (CCB), lercanidipine, are presented. Results of these trials show the firm position of lercanidipine in the modern cardiology and confirm that treatment with lercanidipine leads to significant reduction of systolic and diastolic blood pressure (BP) with no effect on heart rate (HR). Peripheral edema (the common side effect of CCBs) occurs rarer with lercanidipine treatment than this with any other CCB treatment. Lercanidipine can be recommended to patients with concomitant diseases due to its additional features.

Cellular and molecular mechanisms of tissue protection by lipophilic calcium channel blockers

Long-acting third-generation dihydropyridine calcium channel blockers (CCBs) improve endothelial dysfunction and prevent cardiovascular events in humans, but their cellular and molecular mechanisms of tissue protection are not elucidated in detail. We assessed organ (renal) protection by the highly lipophilic CCB lercanidipine in a double-transgenic rat (dTGR) model with overexpression of human renin and angiotensinogen genes. We randomly treated dTGR with lercanidipine (2.5 mg/kg/day; n=20) or vehicle (n=20) for 3 wk. Furthermore, we explored the influence of lercanidipine on protein kinase C (PKC) signaling in vivo and in vitro using endothelial and vascular smooth muscle cell cultures. Cumulative mortality was 60% in untreated dTGR, whereas none of the lercanidipine-treated animals died (P<0.001). We found significantly less albuminuria and improved renal function in lercanidipine-treated dTGR (both P<0.05). Lercanidipine treatment also significantly (P<0.05) reduced blood levels of the endogenous NOS inhibitor asymmetric dimethylarginine. On histological examination, we observed significantly less tissue inflammation and fibrosis in lercanidipine-treated animals (both P<0.05). Lercanidipine significantly inhibited angiotensin (ANG) I-mediated PKC-alpha and -delta activation in vivo and in vitro, partly due to reduced intracellular calcium flux. As a result, lercanidipine improved endothelial cell permeability in vitro. Lercanidipine prevents tissue injury and improves survival in a model of progressive organ damage. These effects may result, at least in part, from inhibition of tissue inflammation as well as improved NO bioavailability. Modulation of PKC activity may be an important underlying intracellular mechanism.

DIFFERENT EFFECTS OF MANIDIPINE AND LERCANIDIPINE ON BLOOD PRESSURE, PERIPHERAL CIRCULATION AND ANKLE OEDEMA IN HYPERTENSIVE PATIENTS

P2.330; Citation: Journal of Hypertension Volume 22, Supplement 2, June 2004, page S244 DIFFERENT EFFECTS OF MANIDIPINE AND LERCANIDIPINE ON BLOOD PRESSURE, PERIPHERAL CIRCULATION AND ANKLE OEDEMA IN HYPERTENSIVE PATIENTS V. Tikhonoff, A. Mazza, E. Casiglia, A.C. Pessina Department of Clinical and Experimental Medicine, University of Padua, Via Giustiniani 2, 35128 Padua, Italy Objectives: To evaluate the oedemigenous effect and the anti-hypertensive efficacy of two newgeneration dihydropyridine calcium channel blockers, manidipine and lercanidipine. Design and Methods: The study was a randomized, controlled, parallel group trial. After a 2-week placebo run-in, 53 mild-to-moderate hypertensive patients aged 18-75 years were treated for 12 weeks with either manidipine (10 mg/day) or lercanidipine (10 mg/day) by oral route in the morning. 24-hour blood pressure (BP) and heart rate were recorded with a TM-2430 device (Takeda, Tokyo, Japan). Leg arterial flow (ml⋅min−1⋅dl−1) was measured with strain-gauge plethysmography (Angioflow, Microlab, Padova, Italy) both at rest and after ischemia, at baseline as well as at the end of treatment. Peripheral resistances (mmHg⋅min⋅dl⋅ml−1) were calculated as the mean BP/flow ratio; minimal arterial resistance calculated from peak flow was taken as an indirect measure of arterial wall thickness. Ankle volume was assessed with water-displacement plethysmography, and ankle oedema calculated for each drug as difference between baseline and post-treatment volume. Results: In comparison to baseline, daytime BP decreased from 147±15/85±7 to 139±16/80±10 mmHg with manidipine (systolic and diastolic: p<0.001) and from 147±12/85±9 to 141±12/79±6 mmHg with lercanidipine (systolic and diastolic: p<0.001). Normalization of BP (<140 and <90 mmHg) was observed in 35% of cases after manidipine and in 18% after lercanidipine (p<0.005 between treatments). HR remained unchanged with both drugs. Rest and post-ischaemic vascular peripheral resistance significantly decreased after manidipine (−30%, p<0.005) but not after lercanidipine. Ankle volume significantly increased (+6.6%) after lercanidipine, whereas no significant increase was observed after manidipine. Conclusions: Both manidipine and lercanidipine were effective in reducing BP; however, the rate of normalization was double with manidipine with respect to lercanidipine. Compared to lercanidipine, manidipine was more potent as a vasodilator and, despite the short-term treatment, reduced arteriolar wall thickness as shown by the reduced maximal arterial resistance. Finally, vasodilatory edema was less pronounced with manidipine than with lercanidipine treatment.

Cardiovascular safety of lercanidipine in patients with angina pectoris: a review of six randomized clinical trials

Background: Lercanidipine, a novel lipophilic and vasoselective dihydropyridine calcium antagonist, is an effective antihypertensive drug at dosages of 10 mg once daily in most patients and at dosages of up to 20 mg once daily in nonresponders. Analysis of a large population of hypertensive patients (2,731,000 patient months) has documented that lercanidipine is well tolerated and is not associated with any serious adverse effects. The safety profile of the compound has also been assessed in patients at higher cardiovascular risk due to existing coronary artery disease. Objective: This article reviews the results of 6 randomized, double-blind, controlled trials of lercanidipine to assess the cardiovascular tolerability of this agent in patients with angina. Methods: After a single-dose study of 37 patients, 263 patients with chronic stable angina were treated with lercanidipine at different dosages (5–30 mg/d) for 3 to 12 weeks in 5 other double-blind, placebo- or active-controlled, randomized studies. Safety data from these trials were reviewed. Results: Analysis of heart rate and blood pressure during treatment, both at rest and during effort, indicates that no negative reflex sympathetic activation or undesirable increase in myocardial oxygen consumption should be expected when using lercanidipine. No sudden drop in blood pressure was observed in the studies reviewed. In all studies, a reduction in the percentage of patients with signs of ischemia or angina during exercise tolerance testing was observed after lercanidipine treatment. Conclusions: Data from 6 randomized clinical trials indicate that lercanidipine can be safely used, even in the presence of stable coronary artery disease such as chronic angina.

Long-term effects of lercanidipine on the lipoprotein and apolipoprotein profile of patients with mild-to-moderate essential hypertension

The goal of this multicenter, randomized, double-masked, parallel- group study was to assess the effects of lercanidipine versus those of hydrochlorothiazide (HCTZ) on the lipoprotein and apolipoprotein profile of patients with mild-to-moderate essential hypertension. After a 2-week washout period, 52 patients (age range, 18 to 70 years) were randomly allocated to receive lercanidipine 10 mg (n = 26) or HCTZ 12.5 mg (n = 26) once a day for 24 weeks. In nonresponding patients, the dose was increased to 20 or 30 mg of lercanidipine once a day and to 25 or 37.5 mg of HCTZ once a day, after 4 and 8 weeks, respectively. To assess long-term effects, patients receiving lercanidipine entered an additional 24-week follow-up period at the end of the controlled phase of the study. At study end, 73% of patients receiving lercanidipine and 52% of patients receiving HCTZ were still receiving the initial dose of 10 mg and 12.5 mg, respectively; only 1 patient in each group had increased to the highest dose. Lercanidipine and HCTZ were equally effective in lowering systolic and diastolic blood pressures; heart rate remained unchanged in both groups. Lercanidipine treatment did not modify the serum concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, or apolipoproteins A-I and B. HCTZ treatment increased triglyceride levels from 94.8 ± 34.3 mg/dL at baseline to 118.5 ± 39.9 mg/dL after 24 weeks, a statistically significant change ( P < 0.05). The lack of any unwanted side effect on the lipid profile by lercanidipine was confirmed during the long-term follow-up period. Results of this study demonstrate that long-term treatment with lercanidipine did not negatively affect the lipid profile in patients with mild-to-moderate essential hypertension, whereas unwanted side effects were seen with the diuretic, even when used at the low doses currently recommended. Lercanidipine consequently can be safely used in patients with hypertension, even when abnormalities in the lipid profile occur.

Efficacy and Tolerability of Lercanidipine in Comparison to and in Combination with Atenolol in Patients with Mild to Moderate Hypertension in a Double-Blind Controlled Study

The efficacy and tolerability of lercanidipine, a new dihydropyridine calcium antagonist, were assessed in comparison with atenolol in a randomized, double-blind, multicenter trial in patients with mild to moderate essential hypertension. After 3 weeks of placebo run-in, 217 eligible patients were divided into two parallel groups receiving either lercanidipine 10 mg or atenolol 50 mgonce a day. Systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) were measured at weeks 4, 8, 12, and 16 of treatment, 24 ± 2 h after the last dose. After the first 4 weeks of treatment, in non-responder patients (DBP >90 mm Hg or reduction < 10 mm Hg compared to baseline) lercanidipine was initially tritated up to 20 mg and atenolol up to 100 mg. Then, after 8 weeks in patients still unresponsive, the two study drugs were combined. After 4 weeks, BP was significantly (p < 0.01) reduced in both treatment groups compared to control values: lercanidipine DBP −10.26 mm Hg, SBP −12.09 mm Hg; atenolol DBP −11.98 mm Hg, SBP −14.69 mm Hg. The changes observed in the lercanidipine group were not significantly different from those observed in the atenolol group. HR did not change in the lercanidipine group, whereas it significantly decreased in the atenolol group. After the first 4 weeks, patients with normalized DBP included 64.7% in the lercanidipine group and 75.5% in the atenolol group. By doubling the dose of the drug in the nonresponding patients, the percentage of normalized patients in the lercanidipine and atenolol groups increased to 82.2 and 85.7% respectively. Adverse events reported included 10.2% and 8.3% in the lercanidipine group receiving 10 and 20 mg respectively, whereas they were 7.2% and 4.1% in the atenolol group receiving 50 and 100 mg, respectively. The severity of the events was generally mild or moderate. The efficacy of lercanidipine and of atenolol in lowering blood pressure in mild to moderate essential hypertension is similar. However, unlike atenolol, lercanidipine is devoid of any effects on HR. The few adverse events observed with lercanidipine treatment confirmed the good tolerability profile of this new calcium antagonist.