mepirodipine and Hypertension

Although it is commonly agreed that all antihypertensive medications have similar efficacy, there are important differences related to safety, tolerability, patient adherence, cost effectiveness and effects on the prevention or retardation of associated disease progression. It is desirable for antihypertensives to have a long duration of action so that once-daily dosing is possible. In addition, antihypertensive medication must be able to be administered concomitantly with other drugs likely to be taken by the patients. This is particularly critical in the elderly population. Barnidipine, a novel, long-acting calcium antagonist, has met these challenges of modern pharmacotherapy. Its once-daily dosing, good tolerability and durable antihypertensive effect contribute to excellent patient adherence and make this drug a valuable addition to the antihypertensive formulary.

Topics: Calcium Channel Blockers; Clinical Trials as Topic; Humans; Hypertension; Nifedipine

Bamidipine is an antihypertensive drug belonging to the dihydropyridine (DHP) group of calcium antagonists. It is available in a modified-release formulation which has a gradual onset of action and is effective in a single daily oral dose of 10 to 20 mg. Bamidipine has selective action against cardiovascular calcium antagonist receptors and its antihypertensive action is related to the reduction of peripheral vascular resistance secondary to its vasodilatory action. The clinical antihypertensive efficacy of barnidipine is similar to that of other DHP calcium antagonists such as nitrendipine and amlodipine, and antihypertensives belonging to other drug classes such as atenolol and enalapril. Barnidipine has been found to be as efficacious and well tolerated as hydrochlorothiazide in the management of hypertension in elderly patients. Barnidipine is generally well tolerated. As with other DHP calcium antagonists, vasodilator adverse events such as headache, flushing and peripheral oedema account for most of the adverse events reported with its use and are usually transient. Oedema is less frequent than with amlodipine and nitrendipine. Its use is not associated with reflex tachycardia.

Topics: Aged; Animals; Area Under Curve; Biological Availability; Calcium Channel Blockers; Hemodynamics; Humans; Hypertension; Intestinal Absorption; Multicenter Studies as Topic; Nifedipine; Randomized Controlled Trials as Topic

Barnidipine is a stereochemically pure dihydropyridine calcium antagonist with a high potency. The drug showed a slow onset and long-lasting vasorelaxating effect in vitro, and strong antihypertensive activity in hypertension models. Barnidipine was shown to have a high vasoselectivity and offered protection in cardiac and renal ischaemia models. The in vitro drug:drug interaction profile suggests a low potential for clinically relevant interactions with concomitant medication. It can be anticipated that barnidipine is an attractive calcium antagonist, offering good blood pressure control without compensatory baroreflex activity.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Dogs; Guinea Pigs; Humans; Hypertension; Nifedipine; Rats; Swine

Barnidipine is a new dihydropyridine calcium antagonist that is presented in modified-release capsules containing a single S-S optical isomer of the molecule. Its characteristics are of interest, as there is evidence of differences in kinetics, dynamics, interactions and safety of individual enantiomers in traditional racemic preparations of calcium antagonists. The safety of barnidipine and its interaction profile are reviewed.. Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I and occur in the early phase of treatment. Furthermore, safety results in elderly patients are comparable with those in the general population, indicating that barnidipine can be used without dose adjustment in elderly hypertensive patients.. Barnidipine has a pharmacokinetic interaction profile that compares favourably with those from other calcium antagonists. The pharmacokinetic properties of barnidipine are unaffected by food. Minor increases in its availability may occur with concomitant use of alcohol or grapefruit juice, but these are unlikely to have clinical relevance. In contrast with several other calcium antagonists, barnidipine does not affect the steady-state kinetics of digoxin, whereas, like other calcium antagonists its bioavailability may be increased by the concomitant administration of cimetidine. In addition, the potential of barnidipine and its major metabolites to affect the metabolism of concomitant medication is unlikely to be of clinical relevance.. The interaction and tolerability profile of barnidipine is well established in all age groups.

Topics: Aged; Calcium Channel Blockers; Drug Interactions; Humans; Hypertension; Middle Aged; Nifedipine

This article reviews the pharmacological profile of the dihydropyridine calcium antagonist (CaA) barnidipine [(+)-(3'S,4S)-3-(1'-benzyl-3'-pyrrolidinyl)-methyl-2,6-dimethyl-4-(m-nit rophenyl)-1,4dihydropyridine-3,5-dicarboxylate x HCl]. The characteristics and potential advantages of its pharmacological selectivity are also outlined. Barnidipine is an L-type CaA with high affinity for [3H]nitrendipine binding sites (Ki = 0.21 nmol/l). Its pharmacological profile has been studied in a variety of isolated tissues and animal models, such as isolated coronary arteries (pig, dog, rat), aorta (guinea pig) and in hypertensive rats (spontaneously hypertensive, renal hypertensive, desoxycorticosterone acetate [DOCA]-salt). Barnidipine may be characterized as a highly potent drug with vasoselectivity and, accordingly, a lack of negative inotropic activity. The onset of its action in vivo is slow, and it does not elicit reflex tachycardia. Its long duration of action, due to its lipophilicity, means that satisfactory control of elevated blood pressure can be obtained with once-daily dosing. Another interesting feature of barnidipine is its stereoselectivity. As the barnidipine molecule contains two chiral centres, it can have four possible enantiomers. The active component in the capsules used clinically consists of the S,S form, which is the most potent and longest acting of the four enantiomers.

Topics: Animals; Calcium Channel Blockers; Dihydropyridines; Dogs; Guinea Pigs; Hypertension; Nifedipine; Rats; Rats, Inbred SHR; Structure-Activity Relationship

Essential hypertension has been extensively reported to cause endothelial dysfunction. The aim of this study was to evaluate the effects of barnidipine or lercanidipine, in addition to losartan, on some parameters indicative of endothelial damage and oxidative stress in hypertensive, type 2 diabetic patients.. One hundred and fifty one patients were randomised to barnidipine, 20 mg/day, or lercanidipine, 20 mg/day, both in addition to losartan, 100 mg/day, for 6 months. We assessed BP every month, in addition, patients underwent ambulatory blood pressure monitoring (ABPM). We also assessed: fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), some markers such as high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), metalloproteinase-2 (MMP-2) and -9 (MMP-9), soluble vascular adhesion protein-1 (sVCAM-1), soluble intercellular adhesion protein-1 (sICAM-1), isoprostanes and paraoxonase-1 (PON-1).. Both barnidipine and lercanidipine resulted in a significant reduction in blood pressure, even if the reduction obtained with barnidipine + losartan was greater than that obtained with lercanidipine + losartan. Data recorded with ABPM also showed a similar trend. Barnidipine + losartan reduced the levels of Hs-CRP, TNF-α, sVCAM-1, sICAM-1, and isoprostanes both compared to baseline and to lercanidipine + losartan.. Barnidipine + losartan gave an improvement of some parameters indicative of endothelial damage and oxidative stress in diabetic and hypertensive patients.. NCT02064218 , ClinicalTrials.gov.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biomarkers; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypertension; Italy; Losartan; Male; Middle Aged; Nifedipine; Oxidative Stress; Time Factors; Treatment Outcome

The aim of this study was to evaluate the effects of barnidipine+losartan compared with telmisartan+hydrochlorothiazide on several parameters of insulin sensitivity in patients with hypertension and type 2 diabetes mellitus. We enrolled 148 normocholesterolemic patients with mild-to-moderate hypertension and type 2 diabetes mellitus. Patients were treated with barnidipine, 20 mg day(-1), in combination with losartan, 100 mg day(-1), or with telmisartan+hydrochlorothiazide, 80/12.5 mg day(-1), for 6 months. We assessed blood pressure (BP) on a monthly basis; additionally, blood samples were collected to assess, at baseline and after 6 months, the following parameters: fasting plasma glucose; glycated hemoglobin; fasting plasma insulin; HOMA index; and some adipocytokines, such as adiponectin (ADN), resistin, leptin, visfatin and vaspin. Patients were also subjected to an euglycemic hyperinsulinemic clamp to assess the M value and glucose infusion rate to ascertain their insulin sensitivity. One hundred and forty-one patients completed the study. The BP was reduced in both groups, although the reduction was greater with barnidipine+losartan (P<0.001 vs. baseline and P<0.01 vs. telmisartan+hydrochlorothiazide). Barnidipine+losartan increased the M value and glucose infusion rate during the euglycemic hyperinsulinemic clamp (P<0.05 vs. baseline and vs. telmisartan+hydrochlorothiazide). With respect to the levels of adipocytokines, ADN was increased (P<0.05), and resistin and leptin were reduced from baseline with barnidipine+losartan (P<0.05 vs. baseline), but they were not reduced with telmisartan+hydrochlorothiazide. Visfatin and vaspin were reduced by barnidipine+losartan compared with baseline (P<0.05). The adipocytokine levels obtained with barnidipine+losartan were significantly better than those obtained with telmisartan+hydrochlorothiazide (P<0.05 for all parameters). In addition to providing a greater BP reduction, barnidipine+losartan improved the insulin sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, and improved some of the adipocytokines related to insulin resistance.

Topics: Adipokines; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Benzoates; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Diuretics; Double-Blind Method; Drug Combinations; Female; Glucose Clamp Technique; Humans; Hydrochlorothiazide; Hypertension; Insulin Resistance; Losartan; Male; Middle Aged; Nifedipine; Telmisartan

The aim of this study was to evaluate the effects of lercanidipine or barnidipine on echocardiographic parameters, in hypertensive, type 2 diabetics with left ventricular hypertrophy. One hundred and forty-four patients were randomized to lercanidipine, 20 mg/day, or barnidipine, 20 mg/day, in addition to losartan, 100 mg/day, for 6 months. We evaluated: blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA(1c)), lipid profile, creatinine, estimated glomerular filtration rate (eGFR), sodium, potassium, and acid uric. Echocardiography was performed at baseline and after 6 months. Both lercanidipine and barnidipine decreased blood pressure. Left ventricular mass index was reduced to a greater extent with barnidipine + losartan. Interventricular septal thickness in diastole was reduced by barnidipine + losartan. Posterior wall thickness in diastole was decreased by both treatments, even if barnidipine + losartan were more effective. Ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction was increased by barnidipine + losartan, but not by lercanidipine + losartan. Finally, isovolumetric relaxation and time and left atrial volume index were reduced by barnidipine + losartan, while lercanidipine + losartan did not affect them. In conclusion, barnidipine + losartan provided a greater improvement of echocardiographic parameters compared to lercanidipine + losartan.

Topics: Aged; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Male; Middle Aged; Nifedipine; Treatment Outcome

The aim of this study was to evaluate the effects of perindopril or barnidipine alone or combined with simvastatin on metabolic parameters and hepatic steatosis degree. One hundred and forty nine mild to moderate hypertensive, normocholesterolemic, overweight or obese outpatients with hepatic steatosis were enrolled. They were treated with perindopril 5mg/day, or barnidipine, 20mg/day, for 6 months; subsequently simvastatin, 20mg/day was added to both treatments for further 6 months. Blood pressure variation was recorded. Patients also underwent an ultrasound examination, at baseline and after 6, and 12 months. We also assessed: fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), tumor necrosis factor-α (ΤΝF-α), interleukin-6 (IL-6), high-sensitivity C reactive protein (Hs-CRP). Both perindopril and barnidipine reduced blood pressure, with barnidipine being more effective. Barnidipine, but not perindopril, slightly decreased total cholesterol and triglycerides after 6 months compared to baseline; lipid profile improved in both groups when simvastatin was added. Regarding inflammatory parameters, barnidipine reduced TNF-a, IL-6, and Hs-CRP, both in monotherapy, and after simvastatin addition. Hepatic steatosis parameters improved only when simvastatin was added. We can conclude that barnidipine better reduced blood pressure compared to perindopril and inflammatory parameters. Regarding hepatic steatosis parameters, only the addition of simvastatin improved them.. NCT02064218, ClinicalTrials.gov.

Topics: Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Hypolipidemic Agents; Male; Nifedipine; Non-alcoholic Fatty Liver Disease; Obesity; Perindopril; Simvastatin

It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p < 0.05). Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.

Topics: Adult; Antihypertensive Agents; Calcium Channel Blockers; Endothelial Cells; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Nifedipine; Stem Cells

BACKGROUND. In hypertensive patients, endothelial dysfunction is associated with an increased incidence of cardiovascular events. Calcium-channel antagonists can reverse impaired endothelium-dependent vasodilation in different vascular districts, while conflicting results are found in the brachial artery. Aim. To investigate the effect of barnidipine in comparison with hydrochlorothiazide on endothelial function of hypertensives, as assessed by flow-mediated vasodilation (FMD) of the brachial artery. METHODS. Patients with mild to moderate hypertension (age range 26-67 years) were randomized to receive barnidipine or hydrochlorothiazide. A thorough clinical examination, including blood pressure (BP) measurement, was performed at randomization as well as after 6, 12 and 24 weeks. FMD and 24-h BP monitoring was performed at randomization, after 12 and 24 weeks. RESULTS. After 12 and 24 weeks of treatment, a significant reduction in clinic BP was observed in both groups. Furthermore, a significant reduction in 24-h SBP and DBP was observed in patients receiving barnidipine but not in those receiving diuretic. The percentage change in FMD was different between the two groups of patients treated with barnidipine (at 12 weeks +1.2 ± 2.2%, p = 0.023 and at 24 weeks +1.25 ± 3.15%, p = 0.16 from baseline) or with hydrochlorothiazide (at 12 weeks -1.0 ± 3.0. p = 0.09 and at 24 weeks -1.78 ± 2.9%, p = 0.015 from baseline). A significant difference in FMD changes between the two groups was confirmed by analysis of covariance (p = 0.031). CONCLUSIONS. In presence of a similar clinic BP reduction, an improvement of endothelial function was observed during treatment with barnidipine but not with hydrochlorothiazide, suggesting that the barnidipine may exert a favourable effect on endothelial dysfunction in hypertensive patients.

Topics: Adult; Aged; Antihypertensive Agents; Brachial Artery; Calcium Channel Blockers; Endothelium, Vascular; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Nifedipine; Vasodilation

Increasing the dose or adding a second antihypertensive agent are 2 possible therapeutic choices when blood pressure (BP) is poorly controlled with monotherapy.. This study investigated the effectiveness and tolerability of barnidipine 10 or 20 mg added to losartan 50 mg versus losartan 100 mg alone in patients with mild to moderate essential hypertension whose BP was uncontrolled by losartan 50-mg monotherapy.. This was a 12-week, multicenter, randomized, open-label, parallel-group study. Eligible patients (aged 30-74 years) had uncontrolled hypertension, defined as office sitting diastolic BP (DBP) > or =90 mm Hg and/or systolic BP (SBP) > or =140 mm Hg, and mean daytime DBP > or =85 mm Hg and/or SBP > or =135 mm Hg. All were being treated with losartan 50 mg at enrollment. After a 1-week run-in period while taking losartan 50 mg, patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg or losartan 100-mg monotherapy. At the end of this period, patients with uncontrolled BP had barnidipine doubled to 20 mg and continued for an additional 6 weeks, whereas patients not achieving control on treatment with losartan 100 mg were discontinued. Office BP was measured at each visit, whereas 24-hour ambulatory BP monitoring (ABPM) was performed at randomization and at the final visit (ie, after 12 weeks of treatment, or at 6 weeks for patients not controlled on losartan 100 mg). The intent-to-treat population included all randomized patients who received at least one dose of study treatment and had valid ABPM recordings at baseline and the final visit. The primary end point was the change in daytime DBP between baseline and 12 weeks of treatment, compared between the combination treatment and monotherapy. Adverse events (AEs) were evaluated during each study visit.. A total of 93 patients were enrolled (age range, 30-75 years; 60% [56/93] men). After the 1-week run-in period, 68 patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg (n = 34) or losartan 100-mg monotherapy (n = 34). A total of 53 patients were evaluable (barnidipine plus losartan, n = 28; losartan, n = 25). After 6 weeks of treatment, 18 patients in the combination treatment group (64.3%) had their dose of barnidipine doubled from 10 to 20 mg because BP was not normalized by treatment, whereas 8 patients in the losartan group (32.0%) were discontinued for the same reason. The between-treatment difference (losartan alone - combination treatment) for changes from baseline in daytime DBP was -1.7 mm Hg (95% CI, -5.8 to 2.4 mm Hg; P = NS). A similar result was observed for daytime SBP (-3.2 mm Hg; 95% CI, -8.1 to 1.7 mm Hg; P = NS). Likewise, no significant differences were found for nighttime values (mean [95% CI] DBP, 0.5 mm Hg [-3.7 to 4.7 mm Hg]; SBP, 1.5 mm Hg [-4.1 to 7.1 mm Hg]) or 24-hour values (DBP, -0.9 mm Hg [-4.8 to 2.9 mm Hg]; SBP, -1.6 mm Hg [-5.9 to 2.7 mm Hg]). Combination treatment was associated with a significantly higher rate of SBP responder patients (ie, <140 mm Hg or a reduction of > or =20 mm Hg) compared with monotherapy (82.1% [23/28] vs 56.0% [14/25]; P = 0.044). Drug-related AEs were reported in 4 patients taking combination treatment (total of 7 AEs, including 2 cases of peripheral edema and 1 each of tachycardia, atrial flutter, tinnitus, confusion, and polyuria) and in 2 patients taking losartan alone (total of 2 AEs, both tachycardia).. This open-label, parallel-group study found that there was no significant difference in the BP-lowering effect of barnidipine 10 or 20 mg in combination with losartan 50 mg compared with losartan 100-mg monotherapy in these patients with essential hypertension previously uncontrolled by losartan 50-mg monotherapy. However, the percentage of responders for SBP was significantly higher with the combination. Both treatments were generally well tolerated. European Union Drug Regulating Authorities Clinical Trials (EudraCT) no. 2006-001469-41.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypertension; Losartan; Male; Middle Aged; Nifedipine

Increased central aortic pressure resulting from large artery stiffening and increased wave reflection is associated with higher hypertension-related morbidity.. The goal of this study was to evaluate the effects of a vasodilator-based therapy with the calcium channel blocker barnidipine on arterial stiffness, wave reflection, and left ventricular (LV) performance using an integrated cardiovascular ultrasound approach (including wave intensity analysis).. Newly diagnosed, previously untreated patients with grade 1 or 2 essential hypertension (systolic blood pressure [BP] > or =140 and <180 mm Hg, and/or diastolic BP > or =90 and <110 mm Hg), and with no signs of clinical cardiovascular disease, were eligible for study. Carotid artery mechanics were investigated at baseline and after 3 and 6 months of barnidipine therapy (10-20 mg once daily, according to an open-label design) using a double-beam carotid ultrasound technique. This provided a simultaneous recording of diameter-derived pressure and flow velocity signals and allowed analysis of wave intensity. Indices of local arterial stiffness and wave reflection, as well as separated forward and backward pressure waves, were estimated. LV geometry, mass, and systolic and diastolic performance were also assessed using Doppler echocardiography. All ultrasound examinations and readings were performed by investigators blinded to patient demographics and treatment phase. Normotensive control subjects (office BP <140/90 mm Hg) were included as a reference group.. Twenty-one white, treatment-naive patients with hypertension (mean [SD] age, 58 [8] years; 14 males; mean body mass index, 27 [5] kg/m(2); mean BP, 159 [14]/96 [5] mm Hg) were enrolled. Twenty normotensive subjects comprised the control group. Compared with the control subjects, patients with hypertension had a higher mean augmentation index ([AIx] 22.0% [7.0%] vs 13.1% [5.2%]; P < 0.01), Peterson's pressure-strain elastic modulus (175 [49] vs 126 [41] kPa; P < 0.01), and forward and backward pressure waves (137 [17] vs 108 [7] mm Hg [P < 0.001] and 21 [6] vs 17 [5] mm Hg [P < 0.05], respectively) at baseline. After 6 months of barnidipine treatment, mean office BP in the patients with hypertension decreased from 159 (14)/96 (5) mm Hg at baseline to 138 (16)/81 (9) mm Hg (P < 0.001) due to a significant reduction in forward and backward pressure waves, and AIx decreased to 17.0% (8.0%) (P < 0.01); there were no significant changes in indices of intrinsic arterial stiffness. A significant direct relationship between AIx and pulse pressure (r = 0.45 [P < 0.05]) was observed at baseline in hypertensive patients but not after therapy (r = 0.26 [P = NS]). Mean stress-adjusted LV midwall shortening increased from 110% (17%) at baseline to 118% (13%) at 6 months (P < 0.05), which was comparable to baseline values in the control subjects (119% [10%]).. In these middle-aged patients with newly diagnosed mild to moderate hypertension, vasodilator therapy with barnidipine reduced central BP by a parallel reduction of forward and backward pressure waves, together with a later arrival of the reflected waves, with no significant changes in intrinsic arterial stiffness.

Topics: Aged; Blood Flow Velocity; Blood Pressure; Calcium Channel Blockers; Carotid Arteries; Echocardiography, Doppler; Elasticity; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Ventricular Function, Left

The effect of barnidipine, a calcium channel blocker, on metabolic parameters is not well known. The authors conducted the present pilot study to evaluate the possible effects of barnidipine on parameters involved in atherogenesis, oxidative stress, and clotting activity. This open-label intervention study included 40 adult patients with essential hypertension who received barnidipine 10 mg once daily. Barnidipine significantly reduced systolic and diastolic blood pressure as well as isoprostane levels, which represent a reliable marker of oxidative stress. In contrast, barnidipine had a neutral effect on lipid profile and apolipoprotein levels, did not influence glucose homeostasis, had no effect on renal function, and did not cause any changes in electrolyte levels. Moreover, barnidipine did not affect either the clotting/fibrinolytic status (evaluated by measurement of fibrinogen, total plasminogen activator inhibitor, tissue plasminogen activator, and a2 antiplasmin) or the enzymatic activity of the inflammatory/anti-inflammatory mediators lipoprotein-associated phospholipase A2 and paraoxonase 1, respectively. Barnidipine should be mainly considered as an antihypertensive agent with neutral effects on most of the studied metabolic parameters in hypertensive patients. Any antioxidant effect of barnidipine needs further investigation.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Antihypertensive Agents; Aryldialkylphosphatase; Blood Coagulation; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Electrolytes; Female; Fibrinolysis; Greece; Humans; Hypertension; Isoprostanes; Kidney Function Tests; Lipids; Male; Middle Aged; Nifedipine; Oxidative Stress; Phospholipases A2; Pilot Projects; Time Factors; Treatment Outcome

To evaluate the effect of barnidipine hydrochloride, a long-acting dihydropyridine calcium channel blocker on urinary sodium excretion in patients with essential hypertension.. Twelve patients (2 males, 10 females) with mild to moderate essential hypertension.. A single-blinded study. After the control (placebo) period, 10 to 15 mg barnidipine hydrochloride was administered for 7 days, followed by a post-treatment (placebo) period. Daily changes in blood pressure, urinary volume, and urinary electrolyte excretions were evaluated. Plasma levels of atrial natriuretic peptide (ANP) and aldosterone were also determined in each period. Daily sodium intake was kept at 120 mEq.. Blood pressure decreased from 161 +/- 4/92 +/- 2 mmHg to 146 +/- 4/85 +/- 2 mmHg (p<0.05) after 7-day-treatment with barnidipine. Barnidipine significantly increased urinary sodium excretion; the change was evident on the first day of administration (control period 41 +/- 3 mEq/day, and first day 59 +/- 3 mEq/day, p < 0.05). Drug discontinuation transiently decreased sodium excretion to 35 +/- 3 mEq/day. Cumulative sodium balance after 7-day-treatment reached 47 +/- 19 mEq. Urine volume, potassium excretion, and creatinine excretion did not change during the treatment period. The plasma levels of ANP tended to increase, but those of aldosterone did not change with barnidipine.. Barnidipine administration for a week decreased the blood pressure and made the sodium balance negative by increasing the urinary sodium excretion in patients with essential hypertension. The natriuretic effect of this drug could contribute at least in part to its antihypertensive effect.

Topics: Adult; Aged; Calcium Channel Blockers; Female; Humans; Hypertension; Male; Middle Aged; Natriuresis; Nifedipine; Single-Blind Method

The objective of this study was to compare the long-term efficacy and safety of 6 months' treatment with barnidipine and hydrochlorothiazide (HCTZ) as monotherapy in patients aged > or = 75 years with mild to moderate essential hypertension. This was a randomised, double-blind, dose-titration study performed at 62 centres in 8 countries. A total of 397 patients were enrolled. Following a 4 week single-blind placebo runin, 315 patients with a sitting diastolic blood pressure (SiDBP) of 95-115 mmHg and a systolic blood pressure of 150-200 mmHg were randomised to receive barnidipine 10 mg (n = 159) or HCTZ 12.5 mg (n = 155) once daily. In patients who had not responded (SiDBP > 90 mmHg) after 6 weeks of double-blind treatment, the dose was titrated upwards to barnidipine 20 mg or HCTZ 25 mg. After 18 weeks, those who did not respond to the higher dose had enalapril (up to 10 mg once daily) added to their regimen. Statistically equivalent reductions in SiDBP were achieved with barnidipine and HCTZ monotherapy. At week 18 of double-blind treatment on monotherapy, 84% of patients in both groups were responders. The addition of enalapril in non-responders produced a further reduction in blood pressure. Both drugs were well tolerated. The incidence of drug-related adverse events was greater in the barnidipine than HCTZ-treated group but they were consistent with vasodilation and were categorised as mild to moderate. In conclusion, barnidipine and HCTZ are well tolerated and have equivalent long-term antihypertensive efficacy in older hypertensive patients. For patients whose blood pressure is inadequately controlled on monotherapy, combination therapy with enalapril is effective.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Diuretics; Double-Blind Method; Drug Therapy, Combination; Enalapril; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Nifedipine; Single-Blind Method; Sodium Chloride Symporter Inhibitors; Treatment Outcome

Two multicentre trials have investigated the efficacy and tolerability of treatment with once-daily barnidipine, in patients with mild to moderate essential hypertension. The long-term efficacy and safety of barnidipine were demonstrated in a long-term, multicentre, open-label study. In total, 106, 79 and 32 patients were followed for the first, second and third year, respectively. Patients received barnidipine at a dose titrated to achieve a sitting DBP > or = 90 mmHg or a decrease in sitting BDP > or = 10 mmHg. If necessary, another antihypertensive agent was added to achieve normalisation of blood pressure. In the first year, normalisation of blood pressure was achieved in 91% of patients. This was maintained in 91% and 81% of patients in the second and third years, respectively. At the end of treatment in both years, over 60% of patients remained on barnidipine monotherapy (10 or 20 mg/day). A low incidence of adverse events possibly or probably related to barnidipine (10 or 20 mg/day) monotherapy was reported in the first and second years with headache, peripheral oedema and palpitations the most commonly reported. In the third year of follow-up, only one adverse event, an ECG abnormality, was considered to be possibly related to the study medication. The effective 24 hour control of blood pressure with barnidipine monotherapy was confirmed in a randomised, double-blind, placebo-controlled, cross-over study of 20 patients. These patients were given 6 week regimens of both barnidipine (20 mg/day) and placebo. Office and 24 hour ambulatory blood pressures were recorded at the end of each treatment phase. Barnidipine lowered blood pressure to a significantly greater extent than placebo both at night and during the day. Adverse events were classified as mild or moderate and fewer adverse events were reported with barnidipine treatment compared with placebo. Barnidipine monotherapy (20 mg/day) is safe and effective in providing 24 hour control of blood pressure. Furthermore, the efficacy and tolerability of barnidipine monotherapy (10 or 20 mg/day) are maintained for at least 2 years.

Topics: Adult; Aged; Blood Pressure; Calcium Channel Blockers; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Treatment Outcome

The long-term (2 year) safety and efficacy of barnidipine was assessed in an open-label, dose-titration, multicentre study of 236 patients aged > or = 75 years with a sitting diastolic blood pressure (DBP) > or = 95 mmHg. All eligible patients started treatment with barnidipine 10 mg once daily. After at least 4 weeks treatment, the dose of barnidipine was titrated upwards to 20 mg daily in patients who did not achieve normalisation of blood pressure (sitting DBP < 90 mmHg). After at least another 4 weeks of treatment an ACE inhibitor or diuretic was added if necessary. Barnidipine monotherapy was the final treatment in 74% of patients in the ITT population (50% barnidipine 10 mg, 24% barnidipine 20 mg). The overall response rate was 84.1% at endpoint. Overall mean sitting DBP decreased by 18.4 mmHg from 102.1 mmHg at baseline to 83.7 mmHg at endpoint. Although a total of 82.2% of patients reported at least one adverse event, only 37.4% of patients experienced an adverse event that was possibly or probably related to the study medication. Many patients experienced adverse events associated with co-existing diseases common in older people. It can be concluded that barnidipine as monotherapy or in combination with ACE inhibitors or diuretics is safe and effective in older patients with essential hypertension.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Nifedipine; Treatment Outcome

Topics: Adolescent; Adult; Aged; Blood Pressure; Calcium Channel Blockers; Double-Blind Method; Humans; Hypertension; Middle Aged; Nifedipine; Nitrendipine; Treatment Outcome

Barnidipine is a new 1,4-dihydropyridine calcium antagonist with a strong and long-lasting vasodilatory effect. In order to assess the haemodynamic profile of the antihypertensive effect of barnidipine, a randomized, double-blind study of barnidipine vs nitrendipine was performed in 24 patients with mild to moderate essential hypertension. Following an initial 4-week placebo period, patients whose sitting diastolic blood pressure (SiDBP) was between 95 and 114 mm Hg, and whose sitting systolic blood pressure was between 150 and 219 mm Hg, were randomized (2:1 ratio) to receive either barnidipine (10 mg) or nitrendipine (10 mg) once daily, for a 6-week double-blind period. Subsequently, patients with an SiDBP of less than 90 mm Hg continued for a second 6-week period with the same monotherapy, while patients with an SiDBP of 90 mm Hg or above received double the dose of antihypertensive treatment for the next 6 weeks. Two-dimensional M- and B-mode echocardiography with Doppler flowmetry was performed at the end of both the placebo and active treatment phases. Barnidipine and nitrendipine reduced blood pressure by the same degree (barnidipine: from 165 +/- 2/100 +/- 1 to 145 +/- 2/89 +/- 1 mm Hg, p < 0.01; nitrendipine: from 163 +/- 3/100 +/- 2 to 143 +/- 7/90 +/- 3 mm Hg, p < 0.01) as a result of peripheral vasodilation. This was not accompanied by reflex neurohormonal activation. Moreover, only in the group receiving barnidipine was a significant decrease in plasma noradrenaline observed, both when the patients were in the supine position (from 298 +/- 27 to 214 +/- 21 pg/ml, p < 0.05) and when they were upright (from 472 +/- 37 to 348 +/- 38 pg/ml, p < 0.05).

Topics: Adult; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Nitrendipine; Reflex; Sympathetic Nervous System; Vasodilation

The antihypertensive effects and tolerance of once-daily barnidipine, a novel dihydropyridine calcium antagonist, were evaluated. A total of 190 patients with a sitting diastolic blood pressure (DBP) of 95-114 mmHg were investigated in this multicenter, double-blind, placebo-controlled, dose-ranging study. After a 4-week single-blind placebo run-in period, patients were randomized to placebo or barnidipine (10 mg, 20 mg, or 30 mg modified release capsules) once daily for 6 weeks. Nonresponders (sitting DBP > or =90 mmHg and a decrease of < 10 mmHg) were treated for an additional 6 weeks with a dose increase of 10 mg. At each clinic visit, sitting and standing blood pressure and heart rate were measured approximately 24 hours after the last dose of study drug was taken. Compared with placebo, barnidipine lowered blood pressure, with a trend toward a dose-response relationship over the dose range 10-30 mg. A dose increment of 10 mg in nonresponders resulted in additional reductions in blood pressure. At the end of the active treatment period, the responder rates were 41% and 57% for 10 mg and 20 mg barnidipine, respectively. Heart rate in both sitting and standing positions was not affected by barnidipine. Treatment with barnidipine was well tolerated, and the incidence of adverse events was dose related and consistent with vasodilatation. In conclusion, barnidipine (10-30 mg) administered once daily is well tolerated and reduces blood pressure in patients with mild to moderate hypertension.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Edema; Female; Flushing; Headache; Humans; Hypertension; Male; Middle Aged; Nifedipine

Hypertension is the leading cause of cardiovascular disease worldwide. Calcium channel blockers are an effective antihypertensive treatment, but frequently hypertension remains uncontrolled for many patients, partly due to tolerability issues.. To assess the tolerability and effectiveness of barnidipine in mild to moderate hypertension patients switching treatment from other calcium channel blockers in daily practice.. BASIC-HT, a prospective real life study, enrolled 20,479 hypertensive patients initiating barnidipine treatment. The present paper focuses on a subgroup of patients in BASIC-HT for whom the previous treatment with amlodipine or lercanidipine was replaced by barnidipine. Tolerability and effectiveness of barnidipine in these patients were assessed at two visits during a 3-month follow up.. In 1710 mild to moderate hypertension patients switching treatment from amlodipine or lercanidipine to barnidipine monotherapy or in combination with other antihypertensive drug classes, mean blood pressure decreased during 3-month follow-up. The mean systolic blood pressure decreased from 153.15 mmHg [95% CI 152.35-153.95] at baseline to 139.20 mmHg [95% CI 138.58-139.82] at visit 3, after 3 months. The mean diastolic blood pressure decreased from 88.85 mmHg at baseline [95% CI 88.36-89.34], to 81.56 mmHg [95% CI 81.20-81.91] at visit 3. Among these patients, 65.4% replaced their initial calcium channel blocker treatment to barnidipine for tolerability reasons. During the follow-up, the main adverse event reported was edema (4.8%). The nature and frequency of events reported in this subgroup of switcher patients were in line with those reported by the total population in BASIC-HT.. This real-life study suggests that replacement of other calcium channel blockers with barnidipine is a valuable therapeutic option, especially when tolerability is an issue.

Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Dihydropyridines; Drug Substitution; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Product Surveillance, Postmarketing; Prospective Studies; Time Factors; Treatment Outcome

Obstructive sleep apnoea (OSA) is considered a cause of secondary hypertension. About 50% of patients with OSA show elevated blood pressure levels. Non-dipper pattern (blunted or absent nocturnal decrease of blood pressure) is frequently observed in patients with OSA and is associated with increased cerebral, cardiovascular and renal events. The aim of this study was to observe the effect of barnidipine calcium channel blocker on these patients.. Forty-one patients (mean age 69 ± 17 years, 18 females) with previously diagnosed OSA (by reduced channel home-based polysomnography) who were not being treated with continuous positive airway pressure (CPAP) because of contraindications or because of patient intolerance or rejection were evaluated. Non-dipper status was defined as the presence of a nighttime fall in systolic blood pressure (BP) which was < 10% that of daytime systolic BP as observed in a previous ambulatory blood pressure (ABP) monitoring. OSA was defined according to the presence of 5 or more episodes per hour of apnoea, hypopnoea or arousal due to respiratory effort. The reproducibility of non-dipping status was confirmed through a second 24-h ABP monitoring performed at baseline. On top of the previous stable treatment regimen (which excluded calcium-channel blockers), a 10 mg dosing of barnidipine hydrochloride at bedtime was added to all subjects during a 12-week period.. Among the 41 non-dipper patients, 32 (78%) showed complete normalization of circadian rhythm. Add-on treatment with barnidipine was generally well tolerated.. Bedtime dosing of the calcium-channel blocker (CCB) barnidipine significantly reduced mean nighttime systolic and diastolic ABP in hypertensive patients presenting with non-dipper pattern and OSA--not on CPAP treatment. Moreover, it restored the previously altered circadian rhythm in the majority of them.

Topics: Aged; Aged, 80 and over; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Circadian Rhythm; Continuous Positive Airway Pressure; Diastole; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Polysomnography; Reproducibility of Results; Sleep Apnea, Obstructive; Systole

Blood pressure (BP) is generally poorly controlled in hypertensive patients. One cause is poor adherence to drugs, which can be improved by treatments combining good efficacy and tolerability. Barnidipine is a strong lipophilic calcium channel blocker (CCB) with efficacy similar to other dihydropyridines.. BASIC HT is an observational study in a large population of patients with essential hypertension to evaluate the tolerability of barnidipine in a real-life setting.. 20479 patients were enrolled in the study. Tolerability and efficacy was assessed at 2 visits during a 3-month period. 20275 patients were included in the analysis.. Adverse events were reported by 10.6% of the patients, leading to treatment discontinuation in 3%. Events were those expected with CCBs. The drop-out rate was 8%. Mean systolic and diastolic pressure decreased from 159.6 to 138.2 and from 92.5 to 81.7 mmHg.. The decrease in BP, is probably due to stimulation of good adherence by barnidipine.

Topics: Adult; Aged; Aged, 80 and over; Calcium Channel Blockers; Female; Humans; Hypertension; Male; Medication Adherence; Middle Aged; Nifedipine; Young Adult

The present study was aimed to investigate the influence of Barnidipine treatment on early stage hypertension by determining the function and morphology of the mesenteric and renal arteries as well as the kidney in N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME)-induced hypertensive rats. Barnidipine (3 mg/kg/day p.o) was applied to rats after 2 weeks of L-NAME (60 mg/kg/day) administration, and continued for the next 3 weeks concomitantly with L-NAME. The systolic blood pressure (SBP) of rats was determined to decrease significantly in Barnidipine treated hypertensive group when compared to that of rats received L-NAME alone. Myograph studies demonstrated that the contractile reactivity to noradrenaline were significantly reduced in both of the resistance arteries while endothelium-dependent relaxations to acethylcholine were significantly diminished particularly in the mesenteric arteries of L-NAME-induced hypertensive rats. The impaired contractile and endothelial responses were completely restored by concomitant treatment of Barnidipine with L-NAME. Histopathological examinations verified structural alterations in the arteries as well as the kidney. Moreover, a decrease in endothelial nitric oxide synthase (eNOS) expression was presented both in the arteries and kidney of hypertensive rats which were increased following Barnidipine treatment. Elevated plasma levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were also reduced in Barnidipine treated hypertensive rats. In conclusion, besides to its efficacy in reducing the elevated SBP, amelioration of vascular function, modulation of arterial and renal eNOS expressions as well as reduction of the plasma levels of oxidative and inflammatory biomarkers are possible supportive mechanisms mediating the favorable implications of Barnidipine in L-NAME-induced hypertension model.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension; Inflammation Mediators; Kidney; Kidney Diseases; Male; Malondialdehyde; Mesenteric Arteries; NG-Nitroarginine Methyl Ester; Nifedipine; Nitric Oxide Synthase Type III; Oxidative Stress; Peroxidase; Rats, Wistar; Renal Artery; Time Factors; Vascular Remodeling; Vasoconstriction; Vasodilation

We developed a videomicroscope system with a charge-coupled device camera and evaluated it in the investigation of the glomerular microcirculation in normal [Wistar-Kyoto (WKY)], spontaneously hypertensive (SHR), and streptoyotocin-induced diabetic rats (STZ). In WKY, the diameter of the afferent arterioles (Af) was 11.9 +/- 0.7 microm and that of the efferent arterioles (Ef) was 8.9 +/- 0.7 microm. Af and Ef in each glomerulus could be visualized simultaneously with continuous recording of blood pressure and renal blood flow. In SHR, Af diameter was constricted to approximately 60% of that in WKY. A dose-dependent dilation of Af and Ef was observed after administration of barnidipine (1-10 microg/kg iv), a calcium channel antagonist, in all three groups. No change was seen in the Af-to-Ef diameter ratio (Af/Ef ratio) in WKY. In SHR, the Af/Ef ratio increased significantly because of the marked dilation of Af after barnidipine administration. In contrast, barnidipine dilated Ef in STZ, causing a significant reduction in the Af/Ef ratio. This system can analyze in vivo glomerular microcirculation and systemic macrocirculation simultaneously, allowing more direct investigation of the characteristics of and acute changes in glomerular microcirculation in pathological animals.

Topics: Animals; Arterioles; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Experimental; Hemodynamics; Hypertension; Kidney Glomerulus; Male; Microcirculation; Nifedipine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renal Circulation; Vasoconstriction; Vasodilation

Topics: Blood Pressure; Calcium Channel Blockers; Humans; Hypertension; Nifedipine

We investigated the effect of barnidipine hydrochloride, a Ca(2+) channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-beta(1) in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR. The glomerular level of TGF-beta(1) mRNA expression was not affected by the treatment. Treatment with barnidipine significantly reduced the excretion of urinary protein. Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Gene Expression; Heart Rate; Hypertension; Kidney Glomerulus; Male; Nifedipine; Organ Size; Proto-Oncogene Proteins c-sis; Rats; Rats, Inbred SHR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Treatment Outcome

Four multicentre trials have investigated the efficacy and tolerability of treatment with once-daily, modified-release capsules of barnidipine, a long-acting dihydropyridine calcium antagonist, in patients with mild to moderate essential hypertension. In two of these trials, the clinical profile of barnidipine was compared with those of amlodipine and nitrendipine, which belong to the same class of drug as barnidipine, in a randomized, double-blind, parallel-group manner. In one study, 37 patients received amlodipine and 79 patients received barnidipine. In a second study, 46 patients received nitrendipine and 96 received barnidipine. In each trial, a 4-week placebo run-in phase was followed by a 12-week comparative phase. Changes in sitting and standing diastolic and systolic blood pressures were assessed, and adverse events were recorded. Both studies demonstrated that the antihypertensive efficacy of barnidipine was equivalent to each comparator agent, but barnidipine tended to produce fewer class I adverse reactions. The long-term efficacy and safety of barnidipine were demonstrated in an open-label study. In total, 106 patients were followed for the first year of the study, during which time they received barnidipine at a dose titrated to achieve a sitting diastolic blood pressure of less than 90 mm Hg; if necessary, another antihypertensive agent was added to achieve normalization of blood pressure. Seventy-nine of these patients, most of whom were maintained on barnidipine monotherapy, were followed for a second year, and 32 patients, all of whom received barnidipine monotherapy throughout the study period, were followed for a third year. Blood pressure normalization after 1 year of follow-up was achieved in 91% of patients, and was maintained for the second and third years in 91% and 81% of patients, respectively. The incidence of adverse events, possibly or probably attributable to barnidipine, was 22%, 14% and 3%, respectively, during each successive year. The suitability of barnidipine for once-daily dosing was confirmed in a randomized, double-blind, placebo-controlled, crossover study of 20 patients. These patients were given 6-week regimens of both barnidipine (20 mg) and placebo, preceding 24-h ambulatory blood pressure monitoring. Barnidipine lowered blood pressure to a significantly greater extent than placebo both at night and during the day. These studies suggest that barnidipine possesses equivalent efficacy to amlodipine and nitrendip

Topics: Antihypertensive Agents; Calcium Channel Blockers; Clinical Trials as Topic; Humans; Hypertension; Multicenter Studies as Topic; Nifedipine; Randomized Controlled Trials as Topic; Treatment Outcome

Calcium antagonists (CaAs) are divided into three structural classes, typically represented by verapamil, diltiazem and nifedipine. As a group, the principal (type I) adverse effects of these drugs relate to the pharmacological action of calcium channel blockade, namely vasodilation, and include dizziness, flushing, palpitations and peripheral oedema. The clinical safety of the new dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical trials, including 2041 patients who have been treated with one or more doses of barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I, occurring in the early phase of treatment. The incidence of serious adverse events and the rate of withdrawals are low. Hence, barnidipine is likely to be well tolerated in general clinical use.

Topics: Aged; Calcium Channel Blockers; Humans; Hypertension; Nifedipine; Treatment Outcome

To assess the effects of a vasodilatory beta-adrenoceptor blocker, nipradilol, and a long-acting Ca channel blocker, barnidipine, on insulin sensitivity.. Insulin sensitivity was determined using a euglycemic hyperinsulinemic clamp technique before and after a 12-week treatment period in eighteen patients with essential hypertension.. Both drugs decreased blood pressure without affecting any serum parameters of glucose and lipid metabolism. Nipradilol significantly augmented glucose infusion rate (GIR) from 3.11+/-0.28 to 4.69+/-0.57mg/kg/min (p=0.027). Barnidipine also increased GIR from 3.91+/-0.43 to 5.29+/-0.43 mg/kg/min (p=0.028). Plasma norepinephrine concentrations significantly increased with barnidipine treatment, while nipradilol had no effect on plasma norepinephrine levels. No adverse events were reported during the study.. These results suggest that vasodilatory beta-blockers such as nipradilol and long-acting Ca channel blockers such as barnidipine may be useful in the treatment of insulin resistant hypertensive patients.

Topics: Adrenergic beta-Antagonists; Blood Pressure; Calcium Channel Blockers; Female; Glucose Clamp Technique; Humans; Hypertension; Insulin Resistance; Male; Middle Aged; Nifedipine; Propanolamines; Vasodilator Agents

We evaluated the effect of barnidipine, a dihydropyridine calcium antagonist, administered once daily in the morning in a dose of 5, 10, or 15 mg on ambulatory blood pressure (BP) in 34 patients (51.3+/-9.6 years). Hypertension was diagnosed based on the clinic BP. The patients were classified into groups according to the ambulatory BP: group 1, dippers with true hypertension; group 2, nondippers with true hypertension; group 3, dippers with false hypertension; and Group 4, nondippers with false hypertension. Barnidipine reduced the clinic systolic BP (SBP) and diastolic BP (DBP) in all groups and significantly reduced the average 24 h ambulatory BP (133.0+/-16.5/90.7+/-12.3 mm Hg v 119.7+/-13.7/81.8+/-10.3 mm Hg, P < .0001 for both SBP and DBP). Barnidipine significantly reduced the daytime ambulatory SBP in groups 1, 2, and 3, but not in group 4, and significantly reduced daytime ambulatory DBP in group 1 but not in groups 2, 3, and 4. Barnidipine significantly reduced the nighttime ambulatory SBP only in group 2 and the nighttime ambulatory DBP in groups 2 and 4. Once-a-day administration of barnidipine influenced 24 h BP on true hypertensives (the ratio of the trough to peak effect > 50%), but had minimal effect on low BP such as the nocturnal BP in dippers and the ambulatory BP in false hypertensives. These findings suggest that barnidipine can be used safely in patients with isolated clinic ("white coat") hypertension and in those with dipping patterns of circadian BP variation whose nocturnal BP is low before treatment.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine

1. The effects of barnidipine on blood flow to major organs and on renal function were investigated in anaesthetized dogs and conscious spontaneously hypertensive rats (SHR), and the results were compared with those for nicardipine, nitrendipine, nisoldipine, manidipine and amlodipine. 2. In anaesthetized dogs, barnidipine (0.3-3 mu g/kg i.v.) dose-dependently decreased blood pressure and increased or preserved blood flow in the vertebral, coronary, femoral and renal arteries. The effect of barnidipine on blood flow was the most potent of the compounds tested. In conscious SHR, barnidipine (0.3-3 mg/kg p.o.) produced a dose-dependent antihypertensive effect and decreased renal vascular resistance. Barnidipine also dose-dependently increased urinary volume. The antihypertensive and diuretic effects of barnidipine were the most potent of the drugs tested. 3. In summary, barnidipine was shown to preserve or increase blood flow to major organs and to produce diuretic activity with a decrease in blood pressure. These findings suggest that barnidipine maintains or promotes renal function at antihypertensive doses.

Topics: Anesthesia; Animals; Antihypertensive Agents; Calcium Channel Blockers; Diuresis; Dogs; Female; Hypertension; Kidney; Male; Nifedipine; Rats; Rats, Inbred SHR; Regional Blood Flow; Renal Circulation; Urodynamics; Vascular Resistance

The occupancy in vivo of cardiovascular and cortical Ca++ antagonist receptors by mepirodipine in spontaneously hypertensive rats (SHR) was investigated. At 0.5, 3 and 6 hr after an oral administration of mepirodipine (3 mg/kg) in SHR, there was a significant (69, 51 and 41%, respectively) decrease in the number of cardiac (+)-[3H]PN 200-110 binding sites (Bmax) compared to control values. At 12 hr later, the Bmax value returned to the control value. On the other hand, the mepirodipine administration had little effect on the dissociation constant (Kd) for cardiac (+)-[3H]PN 200-110 binding except at 0.5 hr, when there was a significant increase in the value, suggesting a change in the density rather than affinity of Ca++ antagonist receptors. In the cerebral cortex of these rats, there was a significant (34%) decrease in Bmax values for (+)-[3H]PN 200-110 binding only at 0.5 hr after mepirodipine administration. In contrast, nifedipine administration had a significant increase in Kd values for cardiac (+)-[3H]PN 200-110 binding without a change in Bmax values. The occupancy of cardiac Ca++ antagonist receptors by mepirodipine correlated significantly with its hypotensive effect in SHR. There was approximately a 39 mm Hg reduction of blood pressure by occupying 50% of these receptors. After an i.v. injection of (+)-[3H]PN 200-110 (15 microCi) to SHR, there was specific binding of the ligand in particulate fractions of heart, aorta, ileum and cerebral cortex, but not liver and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Binding Sites; Blood Pressure; Brain; Calcium Channel Blockers; Calcium Channels; Dihydropyridines; Hypertension; Isradipine; Male; Myocardium; Nifedipine; Rats; Rats, Inbred SHR; Receptors, Nicotinic

To evaluate the role of regional hemodynamics in the anti-hypertensive effect of mepirodipine, a new dihydropyridine-derivative calcium antagonist, we measured systemic, renal, hepatic, and forearm hemodynamics in 10 patients with essential hypertension treated with mepirodipine (15 mg/day) for 4 weeks. After the administration of mepirodipine, a significant decline in mean blood pressure (-13.8 +/- 2.3%, p less than 0.01) accompanied by a decrease in systemic vascular resistance (-21.1 +/- 2.6%, p less than 0.01) was observed. Although forearm vascular resistance did not change significantly, both renal (-19.2 +/- 6.7%, p less than 0.01) and hepatic vascular resistance (-17.6 +/- 3.8%, p less than 0.01) decreased considerably. The decrements of mean blood pressure with mepirodipine did not correlate with those of hepatic or forearm vascular resistance but correlated positively with those of renal vascular resistance (r = 0.699, p less than 0.05). Moreover, the increment of renal blood flow with mepirodipine was negatively correlated with the pretreatment level of renal blood flow (r = -0.670, p less than 0.05); renal blood flow increased to a greater extent in patients with lower pretreatment renal blood flow. These findings suggest that the oral administration of mepirodipine in patients with essential hypertension can produce selective vasodilation in the renal vasculature, which may play an important role in the relatively long-term antihypertensive effect of this drug.

Topics: Adult; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Forearm; Hemodynamics; Humans; Hypertension; Liver Circulation; Middle Aged; Nifedipine; Renal Circulation; Vascular Resistance

1. Effects of consecutive administration of YM-09730-5, (3S)-1-benzyl-3-pyrrolidinyl-methyl (4S)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxy lat e hydrochloride, a new calcium antagonist, for 9 wk on blood pressure and urinary excretion of electrolytes were studied in stroke-prone spontaneously hypertensive (SHRSP) rats. 2. YM-09730-5 (1 and 3 mg/kg per day, p.o.) prevented development of hypertension and produced a significant reduction in blood pressure from the first week of the experiment. Nicardipine (15 mg/kg per day, p.o.) produced almost the same degree of antihypertensive effect as YM-09730-5 at a dose of 3 mg/kg. 3. YM-09730-5 produced significant diuresis and increased urinary excretion of electrolytes throughout the experiment. 4. Chronic administration of YM-09730-5 (3 mg/kg) reduced the severity of glomerular lesions in the kidney and vasculitis in the mesenteric artery. 5. These results demonstrate that YM-09730-5 is a potential antihypertensive drug with a potency about 5 times higher than that of nicardipine.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cerebrovascular Disorders; Diuresis; Diuretics; Heart Rate; Hypertension; Male; Nicardipine; Nifedipine; Organ Size; Rats; Rats, Inbred SHR; Renin; Urodynamics