The Protective Effect of Lercanidipine on Indomethacin-Induced Gastric Ulcers in Rats

Abstract Nonsteroidal anti-inflammatory drugs (NSAID) are among the aggressive factors causing gastric ulcer. They cause oxidative damage in the gastric tissue and lead to intracellular calcium deposition. Lercanidipine is a calcium channel blocker derived from the third generation dihydropyridine. The aim of this study is to analyse the effect of lercanidipine on indomethacin-induced gastric ulcers. A total of 24 albino Wistar male rats were divided into four groups; those who received indomethacin 25 mg/kg (IND), 5 mg mg/kg lercanidipine +25 mg/kg indomethacin (LC-5), 10 mg/kg lercanidipine+25mg/kg indomethacin (LC-10) and healthy rats who received 0.5 mL distilled water. Six hours after the application of indomethacin, the animals were sacrificed by high dose thiopental sodium. The stomachs of the animals were excised to perform a macroscopic analysis and the ulcerous region was measured on millimeter paper. All the stomachs were subjected to a biochemical analysis. Macroscopic analysis revealed hyperaemia on the gastric surface of the indomethacin group. Ulcerous tissues formed by oval, circular or irregular mucosal defects in varying diameters and depths were observed on the whole surface of the stomach. Hyperaemia was lower and ulcerous region was smaller in groups LC-5 and LC-10 compared to IND group. Malondialdehyde and myeloperoxidase levels were significantly lower and total glutathione and cyclooxygenase-1 activity were higher in groups LC-5 and LC-10. Lercanidipine did not change the cyclooxygenase-2 activity. Lercanidipine in doses 10 mg/kg is more effective compared to 5 mg/kg. Lercanidipinine can be useful in the treatment of NSAID-induced gastric damage.

Practice of Indian Physicians Towards Use of Calcium Channel Blockers in the Management of Hypertension : A Paper Based Questionnaire Survey.

Hypertension is a prevalent condition. Improving blood pressure control would depend on understanding concerns and limitations of physicians. Objective: Understanding practice of calcium channel blockers use among physicians. Material and methods: A cross-sectional, observational paper based questionnaire survey among 218 Indian physicians. Results: According to 55.83% of physicians (n=218), prevalence of hypertension ranges between 21-40%. Sixty percent physicians get referred cases mostly from the general physicians (69.48%). More than 20% patients have concomitant illness according to 33.81% physicians, most common being diabetes (33.44%).According to 96.30% physicians, due to asymptomatic nature, hypertension remains undiagnosed, untreated and uncontrolled. Stress (32.35%), obesity (23.13%), physical inactivity (22.78%) and smoking (20.52%) are responsible for sympathetic over activity. Calcium channel blockers (CCBs) (37.19%), beta blockers (30.43%), angiotensin receptor blocker (ARB) (12.14%) and angiotensin converting enzyme (ACE) inhibitors (4.02%) are used as first choice in patients with sympathetic over activity. Ischemic event, stroke, heart failure and renal failure occur due to ignoring sympathetic over activity according to 30.91%, 25.39%, 20.97% and 22.30% physicians respectively. According to 51.63% of physicians, patient compliance to antihypertensive therapy is > 70%. Lack of awareness (40.5%) and dosage frequency (24%) are two most common reasons for noncompliance. According to 89.72% of physicians, the current CCBs primarily inhibit L-type calcium channels but cause sympathetic over activity. A total of 48.34% physicians, >10% patients complain of pedal edema with amlodipine. In physicians opinion, blockage of L and N type of calcium channels (56.47%), unique mode of action (11.76%), arteriolar and venous dilation (9.41%) and inhibition of reninangiotensin- aldosterone (RAS) system (7.06%) are responsible for less pedal edema with cilnidipine. A total of 98.7% and 99.54% physicians rated efficacy and safety of cilnidipine as “good-very good” compared to other CCB respectively. Conclusion: In hypertension, sympathetic over activity may cause many complications. As per the physicians opinion survey, cilnidipine because of its unique mechanism of action offers multiple benefits in hypertensive patients and can be preferred over amlodipine.

Simple and effective HPLC method development and its validation for clindipine in human drug free plasma

Simple and effective high performance liquid chromatographic [HPLC] method was developed for estimation of Clindipine in drug free human drug free blank plasma. The internal standard used as Nifidipine [IS]. The current method was used protein precipitating extraction of Clindipine from blank plasma. Separation was achieved on reversedphase c[18] column [25cm × 4.6mm, 5 micro] and the detection was monitored by UV detector at 260 nm. The optimized mobile phase was used acetonitrile: 5mM potassium dihydrogen orthophosphate [pH 4.5], in the ratio of 60:40% v/v at a flow rate of 1.0 ml/min. This linearity was achieved in this method range of 10.0-125.0 ng/ml with regression coefficient range is 0.99. The present method is suitable in terms of precise, accurate and specific during the study. The simplicity of the method allows for application in laboratories that lack sophisticated analytical instruments such as LC-MS/MS or GC-MS/MS that are complicated, costly and time consuming rather than a simple HPLC-UV method. The present method was successfully applied for pharmacokinetic studies

Siderochelins with anti-mycobacterial activity from Amycolatopsis sp. LZ149 / 中国天然药物

Three new compounds, namely siderochelins D (2), E (3), and F (4), together with one known siderochelin A (1), were isolated from Amycolatopsis sp. LZ149 and elucidated by spectroscopic analyses including1D- and 2D-NMR and X-ray single crystal diffraction. Compounds 1-3 showed antibacterial activity against Mycobacterium smegmatis.

Effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism.</p><p><b>METHODS</b>Raji cells were treated with different concentrations of AZD8330. CCK-8 was used to detect the cell viability. The apoptosis rate of Raji cells was detected by flow cytometry using Annexin V/PI-staining. Real-time PCR was used to assess the expression of Bcl-2, Bcl-xl, caspase-3 and VEGF genes. The protein expression level of Bcl-2, Bcl-xl, caspase-3 and p-ERK1/2 was tested with Western blot.</p><p><b>RESULTS</b>The cell survival rate decreased to(62.09±0.86)%,(50.06±1.33)% and (39.13±2.34)% respectively after cells were treated with AZD8330 at 1.00 μmol/L in vitro for 24 h, 48 h and 72 h, and statistically significant differences were observed in groups with different time of treatment(P<0.05). Apoptosis of cells treated with AZD8330 at 0.10, 1.00, 10.00 μmol/L in vitro for 24 h, 48 h and 72 h was analyzed, and the statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). AZD8330 induced Raji cell apoptosis and upregulated expression of Bcl-2, Bcl-xl, VEFG and decreased the expression of caspase-3 in a dose and time dependent manner, and statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). At the same time, the Bcl-2, Bcl-xl and p-ERK1/2 proteins expression is suppressed obviously, but the expression of caspase-3 protein increased.</p><p><b>CONCLUSION</b>AZD8330 induces cell apoptosis by down-regulating the activation of ERK1/2 signal transduction pathway in Burkitt's lymphoma cell line Raji cells in a dose and time dependent manner.</p>

Effect of AZD8330 on proliferation and apoptosis of multiple myeloma cells / 中国实验血液学杂志

This study was aimed to investigate the effect of MEK inhibitor AZD8330 on proliferation and apoptosis of multiple myeloma IM9 and NCI-H929 cell lines and its possible mechanism. These two cell line cells were exposed to different concentrations of AZD8330 for 48 h. The CCK-8 assay was used to detect cell viability and the IC50 value at 48 h. These above-mentioned IM9 and NCI-H929 cells were treated with 5,10 and 100 nmol/L of AZD8330, then the change of cell cycle was analysed by flow cytometry with PI staining. The Wester blot was used to detect the expression levels of cyclin D and cyclin E, and multiple myeloma cells were treated with 10, 100, 1000 and 2000 nmol/L of AZD8330, the AnnexinV/7-AAD double staining was used to analyse cell apoptosis and the Western blot was used to detect the expression level of caspase-3. The results showed that AZD8330 could significantly inhibit the cell viability of IM9 and NCI-H929 cell lines in a time-and dose-dependent manner, the IC50 value (48 h) of IM9 and NCI-H929 were 19.88 ± 2.7 nmol/L and 29.3 ± 2.03 nmol/L respectively, these two cell lines were arrested on G1 phase of cell cycle, the apoptosis cells increased along with enhancement of AZD8330 concentration, and the expression level of cleaved caspase-3 protein was up-regulated. It is concluded that AZD8330 can efficiently inhibit the proliferation of NCI-H929 and IM9 cell lines, and induce apoptosis, suggesting that the AZD8330 may be a potential chemotherapeutic candidate for multiple myeloma therapy.

Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers

PURPOSE: Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements. MATERIALS AND METHODS: We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure. RESULTS: Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1+/-74.1 vs. 215.0+/-69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU> or =275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype. CONCLUSION: CCBs inhibit the antiplatelet activity of clopidogrel.

Preparation, characterization and tableting of cilnidipine solid dispersions

Solid dispersion technique has been developed many years for improving solubility of water-insoluble drugs, aiming to achieve a better oral bioavailability. However, this technique exhibits many inconveniences when used for large-scale tableting procedures. The objective of current research work was to develop cilnidipine solid dispersions [SDs] to improve the dissolution behaviors of this water-insoluble drug. Moreover, an innovative granulation method was designed to simplify the traditional tableting technology used in solid dispersion technique. Three different kinds of polymers, polyethylene glycol [PEG], polyvinylpyrrolidone [PVP] and poloxamer, were used as carriers to prepare solid dispersions. The interactions in the solid state were characterized by differential scanning calorimetry [DSC], powder Xray diffraction [PXRD] and FT-IR spectroscopy. The designed granulation method was employed to prepare solid dispersion tablets and the formulation was optimized through investigating the dissolution behaviors. The results indicated PEG solid dispersion showed the best effect both on physical characterizations and dissolution studies. Furthermore, all type of solid dispersions significantly improved the dissolution rates when compared to pure drug and its corresponding physical mixture [PM]. The solid dispersion tablets prepared in simplified tableting method exhibited better operability, stability and dissolution behavior than the tablets prepared in traditional ways, which brought more opportunities to solid dispersion technique for industrial production

Benidipine has effects similar to losartan on the central blood pressure and arterial stiffness in mild to moderate essential hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Central blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease. Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality. The effects of benidipine, a unique dual L-/T-type calcium channel blocker, on central BP have not been reported. This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives.</p><p><b>METHODS</b>This 24 weeks, multi-center, open label, randomized, active drug comparative, parallel group study was designed as a non-inferiority study. The eligible patients (n = 200) were randomly assigned to receive benidipine (n = 101) or losartan (n = 99). Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP, pulse wave velocity (PWV) and augmentation index (AIx). We also measured the metabolic and inflammatory markers.</p><p><b>RESULTS</b>After 24 weeks, the central BP decreased significantly from baseline by (16.8 ± 14.0/10.5 ± 9.2) mmHg (1 mmHg = 0.133 kPa) (systolic/diastolic BP; P < 0.001) in benidipine group and (18.9 ± 14.7/12.1 ± 10.2) mmHg (P < 0.001) in losartan group respectively. Both benidipine and losartan groups significantly lowered peripheral BP (P < 0.001) and AIx (P < 0.05), but there were no significant differences between the two groups. The mean aortic, brachial and femoral PWV did not change in both groups after 24-week treatment. There were no significant changes of the blood metabolic and inflammatory biomarkers in each group.</p><p><b>CONCLUSION</b>Benidipine is as effective as losartan in lowering the central and peripheral BP, and improving arterial stiffness.</p>

Efficacy and safety of the treatment: combination of benazepril/lercanidipine vs. benazepril alone in patients with mild-to-moderate hypertension / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Combination therapy is an effective method to reduce the blood pressure (BP) for patients with hypertension. This study was performed to evaluate the efficacy and safety of benazepril/lercanidipine compared with benazepril alone in patients with mild-to-moderate hypertension.</p><p><b>METHODS</b>One hundred and eighty-one patients with mild-to-moderate primary hypertension were assigned in this randomized, single-blind, parallel-group study and were randomly divided into group A (benazepril 10 mg/lercanidipine 10 mg) and group B (benazepril 10 mg) for 8 weeks. At 4 weeks, the dosage of Benazepril was titrated up to 20 mg if the diastolic blood pressure (DBP) remained ≥ 90 mmHg. BP control and side effects were evaluated at the end of 1, 4 and 8 weeks.</p><p><b>RESULTS</b>The baseline characteristics of the two groups were similar. The BP in both groups decreased from the baseline (P < 0.05). At the end of 4 and 8 weeks, Benazepril/Lercanidipine produced greater BP reduction than Benazepril alone (P < 0.05). The comparison of the rate of BP control for the benazepril/lercanidipine and benazepril groups at the end of 1, 4, and 8 weeks were 41.2% vs. 37.6% (P > 0.05), 67.1% vs. 44.7% (P < 0.05), and 71.8% vs. 45.9% (P < 0.05). There was no significant difference of side effects between the two groups.</p><p><b>CONCLUSION</b>The benazepril/lercanidipine combination is more effective in reducing BP than benazepril alone, while it does not increase the incidence of side effects.</p>

Antibacterial & antitoxic effects of the cardiovascular drug lacidipine in an animal model.

Background & objectives: Vibrio cholerae produces acute infection by liberating potent enterotoxin, called cholera toxin in human intestine. Cardiovascular drug lacidipine possessing powerful in vitro action against V. cholerae was tested to determine its possible activity against a toxigenic V. cholerae strain in an established animal model. Methods: In the rabbit intestine four loops were constructed, 3 of which were injected with over night grown V. cholerae 569B culture. Of these, two loops were simultaneously given graded doses (100, 200 μg) of lacidipine, one was left as such for a positive control. The first loop received sterile medium (negative control). After 18 h, contents of all the loops were examined for accumulation of fluid and number of viable cells. Results: Lacidipine when administrated with live V. cholerae 569B, caused a reduction in the number of viable bacteria along with amount of fluid in the loops. The amount of fluid and number of viable cells were much reduced in the loop that had 200 μg of lacidipine than the loop that received 100 μg of the drug. Interpretation & conclusions: Lacidipine has distinct inhibitory action against V. cholerae 569B with respect to both viability and production of cholera toxin in the rabbit ileum. Structural modifications of this compound may possibly lead to procurement of new potent antimicrobial drugs.

Efonidipine, Another Beauty Relieving the Pressure

No abstract available.

Effect of an L- and T-Type Calcium Channel Blocker on 24-Hour Systolic Blood Pressure and Heart Rate in Hypertensive Patients

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the effects of an L- and T-type calcium channel blocker (CCB) on 24-hour systolic blood pressure (24-hour SBP) and heart rate (24-hour HR) profiles in essential hypertensive patients. SUBJECTS AND METHODS: Thirty-seven consecutive patients were enrolled in this study. The 24-hour SBP and HR were recorded before and after treatment with efonidipine (L- and T-type CCB, 40 mg), after waking. Changes in 24-hour SBP and HR and the diurnal to nocturnal SBP ratio were measured. The best-fit curves of changes in SBP and HR were depicted using a periodic function. RESULTS: The mean 24-hour SBP and HR decreased significantly after treatment. The diurnal to nocturnal SBP ratio in dipper-type hypertension cases decreased from 16.7+/-6.1% to 8.3+/-9.8% (p<0.05), whereas in non-dipper hypertension cases, it increased from 2.3+/-2.9% to 7.7+/-5.1% (p<0.01). The antihypertensive effect was minimal at 5.0 hours after drug administration and it slowly recovered at a constant rate (2.1 mm Hg/h) over 12 hours in dipper cases. The median 24-hour changes in HR in the dipper and non-dipper cases were -2.3/min and -5.4/min, respectively. A continuous reduction in the change in HR was seen from 3.5 to 23 hours after drug administration. CONCLUSION: The antihypertensive action of efonidipine was characterized by a slow recovery of the SBP decrease at a constant rate (2.1 mm Hg/h) and a non-administration time dependent reduction in 24-hour HR.

Comparison of Pharmacokinetic Characteristics and the Safety between Amlodipine Maleate Tablet 5 mg and Amlodipine Besylate Tablet 5 mg

BACKGROUND: Amlodipine is a third-generation dihydropyridine calcium channel blocker for treating hypertension. Though marketed primarily as a besylate salt, there have been some efforts to find other comparable salts. Among them, maleate is the salt that has been considered favorable for many drugs. The aim of this study was to compare the pharmacokinetics, as well as safety and tolerability of amlodipine maleate with amlodipine besylate. METHODS: This study was open, randomized, two-period crossover design investigated in twelve healthy male volunteers over a 144 h period after administrating two forms of amlodipine 5 mg, respectively. Each period was separated with 2 weeks. Plasma concentrations of amlodipine were determined by liquid chromatography-tandem mass spectrometry. Safety profiles were assessed by vital signs, physical examinations, electrocardiograms, laboratory testing and adverse events monitoring. RESULTS: All subjects were completed this study. Geometric mean ratios (GMRs) of amlodipine maleate/amlodipine besylate of Cmax and AUClast for amlodipine were 0.92 (90 % confidence interval, 0.81 ~ 1.05) and 1.05 (0.96 ~ 1.16), respectively. No serious adverse events were reported, and no clinically relevant changes were observed in safety profiles during this trial. CONCLUSION: Pharmacokinetics, tolerability and the safety were comparable between amlodipine maleate and amlodipine besylate in healthy individuals.

Intracisternal Administration of Voltage Dependent Calcium Channel Blockers Attenuates Orofacial Inflammatory Nociceptive Behavior in Rats

Voltage dependent calcium channel (VDCC), one of the most important regulator of Ca2+ concentration in neuron, play an essential role in the central processing of nociceptive information. The present study investigated the antinociceptive effects of L, T or N type VDCC blockers on the formalin-induced orofacial inflammatory pain. Experiments were carried out on adult male Sprague-Dawley rats weighing 220-280 g. Anesthetized rats were individually fixed on a stereotaxic frame and a polyethylene (PE) tube was implanted for intracisternal injection. After 72 hours, 5% formalin (50 microL) was applied subcutaneously to the vibrissa pad and nociceptive scratching behavior was recorded for nine successive 5 min intervals. VDCC blockers were administered intracisternally 20 minutes prior to subcutaneous injection of formalin into the orofacial area. The intracisternal administration of 350 or 700 microg of verapamil, a blocker of L type VDCC, significantly decreased the number of scratches and duration in the behavioral responses produced by formalin injection. Intracisternal administration of 75 or 150 microg of mibefradil, a T type VDCC blocker, or 11 or 22 microg of cilnidipine, a N type VDCC blocker, also produced significant suppression of the number of scratches and duration of scratching in the first and second phase. Neither intracisternal administration of all VDCC blockers nor vehicle did not affect in motor dysfunction. The present results suggest that central VDCCs play an important role in orofacial nociceptive transmission and a targeted inhibition of the VDCCs is a potentially important treatment approach for inflammatory pain originating in the orofacial area.

Effect of Efonidipine on Proteinuria in Patients with Chronic Kidney Disease Receiving RAS Blockade / 대한신장학회지

PURPOSE: Efonidipine, which inhibits both T- and L-type calcium channels, has been shown to be effective in reducing proteinuria and preserve renal function. This study was conducted to compare the effects of efonidipine versus amlodipine on the management of hypertension and proteinuria in patients with chronic kidney disease (CKD) receiving ACE inhibitors or ARB. METHODS: This study included 41 CKD patients who were at stages 2-4 and had a urine spot protein/ creatinine ratio of >0.5. Patients were administered amlodipine (5 mg/day) and efonidipine (40 mg/ day) for 3 months in a cross-over design. Blood pressure and spot urine protein/creatinine ratio were compared before and after the cross-over treatment. RESULTS: There were 24 male patients and 17 female patients. The mean age of the patients was 55.9+/-12.9 years. When the patients' medication was changed to eponidifine, we obtained the following results. First, there were no significant changes in blood pressure and serum creatinine. Second, the urine spot protein/creatinine ratio was significantly decreased (before the cross-over, 2.9+/-2.6; after the cross-over, 2.3+/-1.9 g/g; p=0.02). Finally, the reduction rate of proteinuria was significantly higher in patients with CKD at stages 2-3 than in those with CKD at stage 4 after the cross-over (stage 2, - 26.1%; stage 3, -17%; stage 4, +12.8%; p=0.03). CONCLUSION: It is concluded that efonidipine may significantly decrease proteinuria compared with amlodipine in CKD patients receiving ACE inhibitors or ARB. Further double-blind clinical trials with a larger sample size are needed to confirm our results.

Renal protective effects of benidipine and valsartan in primary hypertension patients with proteinuria / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the renal protective effects between calcium channel blocker benidipine and angiotensin II receptor blocker valsartan in primary hypertension patients with proteinuria.</p><p><b>METHODS</b>A total of 236 patients were divided to low (< 1 g/24 h) and high (1 - 3 g/24 h) proteinuria groups and treated with benidipine (8 mg/d) or valsartan (80 mg/d) for 48 weeks. Blood pressure, glomerular filtration rate (GFR) and 24 h protein were measured at baseline, 12, 24 and 48 weeks.</p><p><b>RESULTS</b>Blood pressure was significantly and equally reduced in all treated groups (all P < 0.05 vs. baseline). GFR was also significantly and equally improved in all treated groups after 24 weeks treatments (all P < 0.05 at 24 weeks and 48 weeks). Proteinuria reduction at 24 and 48 weeks was more significant in patients treated with valsartan compared to patients treated with benidipine in low proteinuria group [24 weeks: (0.27 +/- 0.07) g/24 h vs. (0.39 +/- 0.06) g/24 h, P < 0.01; 48 weeks: (0.18 +/- 0.01) g/24 h vs. (0.30 +/- 0.05) g/24 h, P < 0.01].</p><p><b>CONCLUSION</b>The renal protection efficacy of valsartan and benidipine was similar in primary hypertensive patients with proteinuria.</p>

Antihypertrophic effect of dihydropyridines calcium channel blockers is dependent on their potential of blocking N-type calcium channel / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the effects of amlodipine, benidipine and nifedipine on myocardial hypertrophy and evaluate the underlying mechanism.</p><p><b>METHODS</b>Myocardial hypertrophy model was created by transverse aortic constriction (TAC) in C57 BL/6 mice, and plasma catecholamine concentrations were measured 7 days after surgery to confirm the sympathetic activation. The 3 drugs were administered in TAC mice for 7 days and cardiac hypertrophy was evaluated according to the heart-to-body weight ratio (HW/BW). Effects of those drugs on the protein synthesis stimulated by phenylephrine in cultured neonatal cardiac myocytes were also examined.</p><p><b>RESULTS</b>HW/BW and plasma concentrations of catecholamine were significantly increased in TAC mice one week after surgery in comparison with to sham-operated mice. One week after TAC, the HW/BW ratio was significantly lower in the amolodipine but not nifedipine-treated group than in the TAC group. Administration of nifedipine via minipump infusion for one week did not decrease HW/BW ratio. Treatment with amlodpine or benidipine, but not nifedipine, decreased the neonatal rat myocyte protein synthesis induced by phenylephrine stimulation.</p><p><b>CONCLUSION</b>Antihypertrophic effect of DHEs on myocardium is dependent on their potential of blocking N-type calcium channel, and the underlying mechanism involves the sympathetic inhibition.</p>

Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension

BACKGROUND AND OBJECTIVES: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. SUBJECTS AND METHODS: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). RESULTS: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 {from 81.5+/-5.3 to 71.8+/-9.9 beats/minute (difference, -9.9+/-9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6+/-8.2 to 132.9+/-13.5 mmHg, p<0.0001; SiDBP: from 96.9+/-5.4 to 88.3+/-8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4+/-13.5 to 133.8+/-11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7+/-8.7 to 87.5+/-9.5 mmHg, p<0.0001). CONCLUSION: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension.

Effect of Lacidipine on Blood Pressure and Endothelial Function in Mild-to-Moderate Essential Hypertension Patients With Diabetes in Korea

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of lacidipine in reducing blood pressure (BP) and to determine its effect on endothelial function in mild-to-moderate hypertensive patients with type 2 diabetes mellitus (DM). SUBJECTS AND METHODS: This was a prospective, multicenter, open-label, single-arm study, enrolling 290 patients with mild-to-moderate hypertension and type 2 DM. Patients were initially treated with 2 mg lacidipine orally once daily for 4 weeks, which was then increased as necessary every 4 weeks to a maximal dose of 6 mg daily. The primary endpoint was the mean change in systolic blood pressure (SBP) from baseline after 12 weeks of treatment. Secondary endpoints included mean changes in diastolic blood pressure (DBP), flow-mediated vasodilatation (FMD), and serum concentrations of biochemical markers such as high-sensitivity C-reactive protein (hs-CRP), monocyte chemo-attractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), and plasminogen activator inhibitor-1 (PAI-1). RESULTS: Lacidipine treatment significantly reduced SBP by -13.4+/-13.0 mmHg (p<0.001) and DBP by -6.2+/-9.3 mmHg (p<0.001). Lacidipine treatment did not improve endothelial-dependent vasodilatation, despite significantly improved nitroglycerin-induced, endothelial-independent vasodilatation. MCP-1 levels significantly decreased from 283.66+/-110.08 pg/mL to 257.83+/-100.23 pg/mL (p<0.001); whereas there were no significant changes in the levels of hs-CRP, MMP-9, or PAI-1. CONCLUSION: Twelve weeks of treatment with lacidipine was effective and well tolerated in mild-to-moderate hypertensive patients with type 2 DM. In spite of inducing a significant reduction in MCP-1 levels, lacidipine did not improve endothelial function.