Effect Of Nilvadipine Research Articles

Effect of Nilvadipine on the Cerebral Ischemia-Induced Impairment of Spatial Memory and Hippocampal Apoptosis in Rats

Effect of Nilvadipine on the Cerebral Ischemia-Induced Impairment of Spatial Memory and Hippocampal Apoptosis in Rats

Effects of nilvadipine, a calcium antagonist, on intimal thickness of vascular grafting in cholesterol-fed rabbits

The effects of nilvadipine on intimal thickness in expanded poly-tetrafluoroethylene grafts were examined in 21 rabbits undergoing infrarenal aorta reconstruction. Seven rabbits received commercial rabbit chow (control group), seven, a regular diet supplemented with 1% cholesterol (cholesterol group); and seven, the cholesterol diet with 98.9% pure nilvadipine 1 mg/kg/day (nilvadipine group). Grafts were harvested 3 months after surgery for histologic examination. Intimal thickness at the proximal and distal anastomosis was, respectively, 225±76 and 273±110 m in the control group, 525±236 and 600±250 m in the cholesterol group, and 284±94 and 241±86 m in the nilvadipine group. Intimal thickness in the cholesterol group was significantly greater than in the nilvadipine group (p<0.01). The smooth muscle cell values in the intima at the proximal and distal anastomosis were, respectively, 10.6±3.6 and 12.6±3.2 %Extinction (%E) in the control group, 15.5±4.0 and 16.1±4.5 %E in the cholesterol group, and 9.1±3.1 and 9.6±2.1 %E in the nilvadipine group. The smooth muscle cell value in the intima of the cholesterol group was greater than that of the nilvadipine group (p<0.01). These data suggest that nilvadipine significantly reduces the degree of intimal thickness in expanded polytetrafluoroethylene grafts in cholesterol-fed rabbits, and that this effect is due to inhibition of smooth muscle cell migration and proliferation.

Effects of nilvadipine and amlodipine in patients with mild to moderate essential hypertension: a double blind, prospective, randomised clinical trial

ABSTRACTObjective: This double blind, prospective, randomised, parallel group clinical trial was aimed at investigating the effects of nilvadipine or amlodipine in mild to moderate hypertensive patients over a 3-month treatment period.Research design and methods: Eligible outpatients (supine DBP ≥ 90 mmHg and ≤ 110 mmHg and supine SBP ≤ 180 mmHg) entered a maximum 15-day placebo run-in period and were randomised to receive once daily nilvadipine 8 mg or amlodipine 5 mg (to be doubled in the case of lack of response at day 30). Follow-up visits with measurement of supine and orthostatic blood pressure and heart rate were performed after 15, 30, 60 and 90 days of treatment. Standard laboratory tests and 12-lead ECG were performed at study entry and at the end of treatment; adverse events were collected at any time.Results: A total number of 168 patients, 83 in the nilvadipine and 85 in the amlodipine group, took part in the study: 15 and 14 in the two groups, respectively, were prematurely withdrawn. Supine DBP at endpoint similarly decreases in the two groups (–11.0 ± 7.1 mmHg in the nilvadipine group and –12.7 ± 8.2 mmHg in the amlodipine group), with no significant differences between groups at any time point. Measurements in the orthostatic position also did not show between-groups differences. Blood pressure was normalised in 61.8% of patients in the nilvadipine group and in 63.0% in the amlodipine group; responders to therapy were 64.5% and 69.1% in the two groups, respectively. Results of SBP also did not show differences between groups at any time point, except a more marked decrease in the amlodipine group compared to nilvadipine in the supine measurements at endpoint. A total number of 30 patients (36.6%) in the nilvadipine group and 23 (27.1%) in the amlodipine group reported adverse events ( p = 0.24 between groups), which mainly consisted of vasodilatory effects (e.g. oedema, flushing and headache). A favourable lipid profile, i.e. a significant ( p = 0.002 between groups) decrease of triglycerides levels and an increase of HDL-C, was observed in the nilvadipine group, compared with an increase of triglycerides in the amlodipine group. No effects on haematology, liver and renal function were observed in either group.Conclusions: Nilvadipine or amlodipine produced comparable effects on DBP and shared a similar adverse effect profile. A favourable effect on lipid profile was observed following nilvadipine treatment.

Effect of Nilvadipine, a Dihydropyridine Calcium Antagonist, on Cytochrome P450 Activities in Human Hepatic Microsomes

The effects of nilvadipine, a dihydropyridine calcium antagonist, on cytochrome P450 (CYP) activities in human hepatic microsomes were investigated. Nilvadipine competitively inhibited CYP1A2-mediated 7-ethoxyresorufin O-deethylase, CYP2A6-mediated coumarin 7-hydroxylase, CYP2C8/9-mediated tolbutamide methylhydroxylase, CYP2C19-mediated S-mephenytoin 4'-hydroxylase, and CYP3A4-mediated nifedipine oxidase activities, and the inhibition constant (Ki) values were 13.0, 35.8, 5.02, 24.5 and 44.3 microM, respectively. On the other hand, no inhibition of CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2D6-mediated bufuralol 1'-hydroxylation, or CYP2E1-mediated chlorzoxazone 6-hydroxylation by nilvadipine at 40 microM concentration was observed. The free fractions of nilvadipine in the incubation mixture estimated by ultracentrifugation were 18.9-27.4%. These results suggest that nilvadipine would not cause clinically significant interactions with other drugs, which are metabolized by CYPs, via the inhibition of metabolism.

2P-0584 Effect of nilvadipine on serum lipoproteins in patients with hypertension

2P-0584 Effect of nilvadipine on serum lipoproteins in patients with hypertension

Effect of nilvadipine on calf- and ankle circumferences in patients with preexisting leg edema

Previous observations suggested, that the long acting calcium entry blocker (CEI) nilvadipine (nilv.) has a low potential to induce leg edema in patients (pts.) with arterial hypertension. We conducted with 261 physicians a prospective study in 1422 pts. (age 60.7 years) with antihypertensive therapy and prior treatment with other CEIs for at least two weeks. CEIs (n=1188: nifedipine)were then (t1) replaced by nilv. at a dose of 8 (62.6%) or 16 (37.4%) mg/d, and leg edema were monitored along with blood pressure (BP) after 4 (t2) and 8 (t3) weeks resp.. Pts on diuretics, with heart failure, renal insufficiency, malnutrition, lymphedema or edema due to varicosis were not included. Syst./diast. BP decreased (p<0.001) by 11.0/6.4 (t2), and 17.2/9.3 (t3) mmHg in all pts. with no difference between male (n=672) and female pts.. Calf circumference (CC) was measured in 668 pts with proven calf edema (63.3%) at all visits, and decreased (p<0.001)from 39.4 ±0.25 (SEM) to 37.6 ±0.24 (t2) and 36.8 ±0.23 (t3) cm. CC decreased in males from 40.5 to 37.8, and in females from 38.6 to 35.9 cm. Ankle edema were reported in 80.4% at start, in 37.6% at t2, and in 15% at the end of the study. Ankle circumference (AC) decreased (p<0.001, n=761) from 29.2 to 27.5 cm (t2), and to 26.7 (t3), with no difference between males and females (-2.5 (t3), and - 2.4 (t3)cm resp.). At the end of the study 32.8 % of the pts. were without complaints regarding edema, 27.6% reported marked, and 25.7% lesser, and 10.3% slight improvement. Replacement of CEI-pretreatment by the dihydropyridine nilv. led to a marked improvement in calf- and ankle circumferences. Edema associated complaints by the pts. were also decreased after nilv. based treatment.

Autoantibody against neuron-specific enolase found in glaucoma patients causes retinal dysfunction in vivo.

In our recent paper, we have reported the presence of serum autoantibody against neuron-specific enolase (NSE) in patients with glaucoma. The purpose of the present study was to investigate further the pathological effects of anti-NSE antibody on retina by comparing them with the effects induced by N-methyl-D-aspartate (NMDA). Either a glaucoma patient's serum or purified anti-NSE antibody, or 10-40 mM NMDA was intravitreously administered into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs, such as timolol, betaxolol, nipradilol, and isopropyl unoprostone, and a calcium antagonist were also studied using these animal models. Electron microscopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50 kDa in Western blot analysis, and purified anti-NSE antibody induced retinal ganglion cell apoptosis in rat eyes. Functionally, these eyes showed a significant decrease in electroretinogram (ERG) responses and a remarkable decrease in rhodopsin phosphorylation reaction. These changes were comparable to the effects observed after the intravitreal administration of 20 mM NMDA. Co-administration of nipradilol, an alpha- and beta-blocker, with anti-NSE antibody or 20 mM NMDA caused marked recovery of the affected ERG responses within 2 weeks. In contrast, administration of timolol or betaxolol showed no recovery effect on the ERG responses. Among these drugs, only betaxolol showed a recovery effect on NMDA-induced decrease of rhodopsin phosphorylation. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phosphorylation reactions observed in rat eyes injected intravitreously with anti-NSE antibody or NMDA. These effects of nilvadipine were not changed by the addition of endothelin-1. In contrast, isopropyl unoprostone had no effect on these functions. These observations suggest that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo, similarly to NMDA.

Effects of Nilvadipine on Retinal Microcirculation and Systemic Circulation

The effects of nilvadipine on retinal blood flow and systemic circulation were studied by the hydrogen clearance method. The subjects were 10 male beagles. Under general anesthesia, nilvadipine (32 micrograms/ml/kg), dissolved in polyethylene glycols was injected into the stomach of 5 beagles, and only polyethylene glycols was injected into the stomach of the other 5 beagles as controls. Retinal tissue blood flow, heart rate, arterial blood pressure, pulmonary arterial pressure, central vein pressure, cardiac output, and systemic vessel resistance were measured over time and compared between the two groups. Retinal tissue blood flow showed significant increase only in the Nilvadipine group (max 29.2%). No marked changes were observed in the systemic circulation in either group. The time to maximum blood concentration of Nilvadipine was 120 min, and the maximum blood concentration was 1.27 ng/ml. Nilvadipine may directly and selectively increase retinal tissue blood flow, while having only minimal effect on systemic circulation including arterial blood pressure.

Nilvadipine protects low-density lipoprotein cholesterol from in vivo oxidation in hypertensive patients with risk factors for atherosclerosis.

Nilvadipine, a calcium antagonist, has been shown to have antioxidant activity in vitro, but its effect on in vivo oxidation has not been assessed. The aim of this study was to investigate the antioxidant effect of this agent in vivo. The ratios of 7-keto cholestadien to cholesterol are believed to be an available marker of lipid peroxidation. Using these ratios, we have assessed the antioxidant effect of nilvadipine on low-density lipoprotein (LDL) in hypertensive patients with high risk of atherosclerosis. The risk factors of atherosclerosis may involve oxidation of LDL. Fifteen healthy subjects (seven females and eight males aged 35-72 years, mean +/- SD = 55.3 +/-13.8 years) and fifteen hypertensive patients (seven females and eight males aged 45-80 years, mean +/- SD = 60.2 +/- 11.8 years) were recruited. Patients were treated orally with nilvadipine (4 mg b.i.d.) for 4 weeks. Cholesterol oxidation levels of LDL in patients before and after nilvadipine therapy and healthy subjects were studied. The ratios of 7-keto cholestadien to cholesterol in LDL of hypertensive patients before and 4 weeks after nilvadipine treatment and in healthy subjects were 6.5 +/- 1.6% (mean +/- SD), 3.8 +/- 1.2%, and 0.2 +/- 0.1%, respectively. There were significantly (P < 0.001) increased levels of cholesterol oxidation in LDL in patients with hypertension both before and after nilvadipine treatment compared with healthy subjects. However, there was a significantly (P < 0.001) decreased level of cholesterol oxidation in LDL in patients after nilvadipine treatment compared with patients before nilvadipine treatment. Our data showed that nilvadipine may protect LDL cholesterol from in vivo oxidation in hypertensive patients with high risk of atherosclerosis.

Effects of Nilvadipine, Nicardipine and Verapamil on Acute Rise of Aqueous Flare Induced by Iris Photocoagulation or Intravenous Lipopolysaccharides in Pigmented Rabbits

The effects of nilvadipine, nicardipine and verapamil on the acute rise of aqueous flare induced by argon laser photocoagulation of the iris or by intravenous injection of lipopolysaccharides (LPS, 0.5 µg/kg) were investigated in pigmented rabbits. Nilvadipine, nicardipine and verapamil were injected intravenously. Aqueous flare was measured with a laser flare cell meter. Following photocoagulation, aqueous flare increased, reached its maximum at 45–75 min and then decreased. After administration of LPS, aqueous flare increased, reached its maximum at 4 h and then returned to baseline levels at about 24 h. Flare reactions were inhibited by nilvadipine in a dose-dependent manner. The elevations were maximally inhibited by nilvadipine 30 min before photocoagulation or intravenous LPS. Two hundred micrograms per kilogram of nilvadipine inhibited 81% of photocoagulation-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 19 and 9% of the elevation, respectively. The same dose of nilvadipine inhibited 51% of LPS-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 6 and 4% of the elevation, respectively. In conclusion, nilvadipine inhibited the experimental elevation of aqueous flare more effectively than did nicardipine and verapamil.

Effects of Nilvadipine on Cytokine-Levels and Soluble Factors in Collagen Disease Complicated with Essential Hypertension

We examined some immunological parameters, particularly cytokines and soluble factors in collagen diseases complicated with essential hypertension. We also investigated the effects of Nilvadipine on immunological parameters after treatment with this drug for six months. The frequency of helper/inducer T cells (CD4+ CD8- cells, CD4+ CD45RA- cells) decreased in the peripheral blood on a 6 month treatment with nilvadipine. There was a significant decrease of suppressor/inducer T cells (CD4+ 45RA+cells), and an insignificant decrease of activated T cells (CD3+ HLA-DR+ cells) and memory T cells (CD45RA- CD45RO+ cells) after treatment. Before treatment with Nilvadipine, interleukin-1 β, tumor necrosis factor-α, and interleukin-6 levels increased higher in the patients than in healthy volunteers. However, interleukin-1 β and interleukin-6 concentrations tended to decrease after treatment with Nilvadipine. Besides, tumor necrosis factor-α decreased significantly after treatment. The soluble interleukin-2 receptor concentrations also showed a decreased tendency after treatment, although high concentrations were found in the patients before treatment.

Comparative Efficacies of a Calcium Antagonist and an Alpha1 Blocker in Elderly Hypertensive Patients with Stroke

We compared the effects of nilvadipine, a calcium antagonist, and terazosin, an alphal blocker, on the hemodynamics and quality of life (QOL) in 12 elderly hypertensive patients with stroke. Following a washout period of 2 weeks, nilvadipine or terazosin was administered for 2 weeks in a randomized crossover manner. At the end of control and treatment periods, we measured the 24-hour ambulatory blood pressure (BP) and postural change of BP, and interviewed QOL. Terazosin treatment did not show consistent decrease of casual BP, but was associated with a transient decrease of systolic BP and an increase of pulse rate after standing, and enhanced postprandial decrease in BP. Nilvadipine decreased casual BP in a dose-dependent manner, but showed neither postural nor postprandial change of BP. There was no difference in QOL scores with either treatment. Results suggest that nilvadipine is preferable to terazosin for the treatment of elderly hypertensive patients with stroke.

Effect of nilvadipine on high-voltage activated Ca2+ channels in rat CNS neurons.

The effect of nilvadipine, a dihydropyridine derivative, on high-voltage activated (HVA) Ca2+ channels was investigated in freshly dissociated rat frontal cortical neurons. The cortical neurons were observed to have five pharmacologically distinct HVA Ca2+ channel subtypes consisting of the L-, N-, P-, O- and R-types. Nilvadipine selectively inhibited the L-type Ca2+ channel current which comprised 23% of the total HVA Ca2+ channel current. A reversible inhibitory effect of nilvadipine on the L-type Ca2+ channel current was also observed in a concentration-dependent fashion without affecting the current-voltage relationship. The half-maximum inhibitory concentration was 3 x 10(-8) M. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca2+ influx, in combination with the cerebral vasodilatory action, may prevent neuronal damage during brain ischemia.

Effects of nilvadipine, a calcium antagonist, on intimal thickness of vascular grafting in cholesterol-fed rabbits

Effects of nilvadipine, a calcium antagonist, on intimal thickness of vascular grafting in cholesterol-fed rabbits

本態性高血圧症における心拍数と血圧と概日変動ならびにＭｏｒｎｉｎｇ Ｒｉｓｅに対するＮｉｌｖａｄｉｐｉｎｅとＣａｐｔｏｐｒｉｌ持効製剤の効果について

本態性高血圧症における心拍数と血圧と概日変動ならびにＭｏｒｎｉｎｇ Ｒｉｓｅに対するＮｉｌｖａｄｉｐｉｎｅとＣａｐｔｏｐｒｉｌ持効製剤の効果について

Effect of nilvadipine and angiotensin-converting enzyme inhibitors on quality of life in patients with essential hypertension: A comparative study

Multicenter, randomized, parallel-group, and open trials were performed in patients with mild-to-moderate essential hypertension to assess the impact of nilvadipine and angiotensin-converting enzyme (ACE) inhibitors on patient quality of life (QOL). After a baseline observation period, 79 patients were enrolled. QOL was evaluated at baseline and at weeks 24, 36, and 52 of treatment. Fourteen patients had withdrawn from the trial by week 24. QOL was assessed in 34 patients treated with nilvadipine and 31 patients treated with ACE inhibitors. Patients receiving nilvadipine reported improvements in headaches and head heaviness, shoulder stiffness, fatigue during work, general well-being, and leisure time enjoyment. Patients receiving ACE inhibitors noted improvements in headaches and head heaviness, shoulder stiffness, irritability, social relationships, and sleep. Nilvadipine was considered better than ACE inhibitors in improving shoulder stiffness and self-control, whereas ACE inhibitors were better than nilvadipine in improving shortness of breath, nocturia, and social relationships. Both nilvadipine and the ACE inhibitors produced similar falls in blood pressure; neither changed heart rate significantly during the treatment period. In conclusion, the two regimens were equally effective in lowering blood pressure with equally favorable effects on QOL.

Therapeutic effects of nilvadipine on rat focal cerebral ischemia.

The present study was conducted to investigate the therapeutic effects of nilvadipine, a Ca2+ entry blocker, on rat focal cerebral ischemia. Under halothane anesthesia, a 3-0 nylon thread was introduced into the neck internal carotid artery to occlude the left middle cerebral artery. Either nilvadipine (3.2 mg/kg) or vehicle was administered subcutaneously 1, 2, 3, 4, 5 and 6 h following the occlusion (groups 1-6, respectively). Twenty-four hours after the occlusion, the percentage infarct volumes in nilvadipine-treated animals in groups 1-3 (21 +/- 11%, 24 +/- 11%, and 26 +/- 7%, respectively) were smaller than those in the respective control groups (36 +/- 5%, 35 +/- 3%, and 35 +/- 3%; P < 0.05). Compared with controls, the infarct size of the periphery of the fronto-parietal cortex decreased in nilvadipine-treated animals. The results indicate that nilvadipine decreases the size of infarction when administered up to 3 h after an ischemic insult. Thus, nilvadipine can be considered a potential therapeutic agent for acute focal cerebral ischemia, and may be clinically useful in stroke patients.

Erythrocyte sodium cannot predict hypotensive effects of calcium channel blockers.

Antihypertensive efficacy of the calcium channel blocker, nilvadipine, was investigated in 21 patients with essential hypertension in relation to the intracellular sodium concentration ([Na]i) in erythrocytes and clinical variables, such as age, body weight, pretreatment blood pressure and plasma renin activity. Dihydropyridine nilvadipine reduced mean blood pressure from 120 +/- 6 to 106 +/- 8 mmHg (p < 0.01). The hypotensive effect of nilvadipine was positively correlated with age (r = 0.67, p < 0.01) and inversely correlated with plasma renin activity (r = -0.62, p < 0.01), but was not correlated with erythrocyte [Na]i or any other indices. Erythrocyte [Na]i was decreased with nilvadipine treatment (8.27 +/- 1.69 to 7.97 +/- 1.49 mM, p < 0.01). However, no link was found between the change in [Na]i and the hypotensive effect of the drug. In conclusion, the antihypertensive efficacy of nilvadipine was predictable by age and renin status, but not by erythrocyte [Na]i. A significant role of reduction of [Na]i in the hypotensive effect of the calcium channel blockers was not detected.

Effect of Nilvadipine on Balloon Catheterization-Induced Intimal Thickening of the Coronary Artery in Miniature Pigs

Summary: The effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery was examined in miniature pigs. A diffuse intimal thickening was observed in vehicle-treated controls 6 weeks after balloon catheterization. The histologic features of the intimal thickening resembled those of early atherosclerotic lesions and restenosis after percutaneous transluminal coronary angioplasty (PTCA). Nilvadipine given in a daily dose of 10 mg/kg (subcutaneously, s.c.) for 6 weeks significantly inhibited intimal thickening. The ratio of the cross-sectional area of the intima to the crosssectional area of the media was significantly reduced by 62% in nilvadipine-treated animals. These results suggest that nilvadipine may prevent or exert beneficial effects on coronary arterial injuries such as atherosclerosis and restenosis after PTCA

Effect of Single Oral Administration of Nilvadipine on Cerebral Blood Flow in Chronic Cerebral Infarction

The effect of nilvadipine, a newly developed calcium antagonist, on regional cerebral blood flow (rCBF) was investigated in 7 patients with chronic cerebral infarction. rCBF was measured by the 133Xenon inhalation method. Patients were given a single dose of 4 mg of nilvadipine after the first measurement of rCBF, and the second measurement was done one hour after the administration. All patients had hemiparesis and 2 of them had mild to moderate mental deterioration, but all patients could walk to the outpatient clinic by themselves. (1) rCBF of the affected side significantly increased by 22.7% after single oral administration of nilvadipine (p < 0.05). The increase of rCBF was significantly marked in frontal regions of the affected hemispheres. (2) No significant changes in blood pressure or end tidal partial pressure of carbon dioxide were observed during the examination. These results indicate that nilvadipine has a potent selective vasodilatory action on the cerebral arteries in patients with cerebral infarction.