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PubMedDate not supplied

The effect of calcium channel blockers and calcium on methotrexate accumulation in rat hepatocytes.

The effects of diltiazem (DIL), verapamil (VRP) and Ca2+ on the accumulation of methotrexate (MTX) were investigated in isolated rat hepatocytes. At the physiological 2 mM Ca2+, the calcium-channel blockers DIL (100 microM) and VRP (50 microM) significantly reduced the hepatocellular accumulation of MTX. By increasing the Ca2+ concentration to 7 mM control MTX levels (at 2 mM Ca2+) were restored with VRP, and resulted in MTX levels above the controls for DIL. Ca2+ at 7 mM significantly enhanced MTX accumulation in the hepatocyte suspensions after 60 min. The concentration time curves for MTX indicated that for the first 10 min influx was the dominating process. Dixon plot analysis of this uptake phase revealed Ki values of 140 microM for DIL and 75 microM for VRP. The data suggested that DIL was a non-competitive, and VRP a competitive inhibitor of MTX influx. Hence, the inhibitory effect on MTX accumulation mediated by DIL and VRP could be due to different mechanisms.

Animals↗
PubMed2003

Effects of antihypertensive agents, alpha receptor blockers, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers, on oxidative stress.

BACKGROUND: Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of hypertension disease (HD). Trace elements function as a co-factor in antioxidant enzymes. The antioxidant system and trace elements have been investigated in many different studies including HD, but these subjects have not been investigated as a whole in these patients. OBJECTIVE: The aim of the present study was to investigate the antioxidative system and trace elements in hypertensive patients given different antihypertensive therapy. METHODS: We examined malondialdehyde and superoxide dismutase activities together with copper and zinc levels in plasma of 102 patients with HD and in 51 healthy controls. RESULTS: It was found that in patients with HD, plasma malondialdehyde was significantly higher than those of controls, while plasma superoxide dismutase activities were significantly lower in patients with HD. Plasma zinc levels were significantly higher than those of controls and plasma copper levels were significantly lower in patients with HD. Plasma lipid levels and oxidative state were analyzed in five different treatment groups given antihypertensive drug therapy before and after a 3-month treatment period. CONCLUSIONS: In conclusion, our clinical study shows that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have notable effects on oxidative stress, and are an essential step in managing essential hypertension by the way of improvement of endothelial dysfunction. Although it has been shown that calcium channel blockers, beta blockers and alpha receptor blockers have antioxidant effects in in vitro conditions, we did not demonstrate these effects in our clinical study.

Adrenergic alpha-Antagonists↗
PubMed1996

Prevalence of use of beta blockers and of calcium channel blockers in older patients with prior myocardial infarction at the time of admission to a nursing home.

OBJECTIVE: To investigate the prevalence of beta blocker use and calcium channel blocker use in older patients with prior myocardial infarction at the time of admission to a nursing home. DESIGN: In a prospective study of 500 consecutive patients aged 60 years or older admitted to a nursing home, 202 (40%) had electrocardiographic evidence of Q-wave myocardial infarction at the time of admission. The prevalence of beta blocker use and of calcium channel blocker use was investigated in these 202 patients with previous myocardial infarction. The prevalence of beta blocker use and of calcium channel blocker use was also investigated in patients with myocardial infarction and abnormal left ventricular (LV) ejection fraction. SETTING: A large long-term health care facility. PATIENTS: The patients included 344 women and 156 men, mean age 81 +/- 8 year (range 60 to 100). MEASUREMENTS AND MAIN RESULTS: Of 500 patients, 202 (40%) had Q-wave myocardial infarction at the time of admission to the nursing home. Seventeen (8%) of these 202 patients with myocardial infarction were receiving beta blockers and 74 (37%) were receiving calcium channel blockers at the time of admission. Of 171 patients with myocardial infarction who had technically adequate measurements of LV ejection fraction, 59 (35%) had an abnormal LV ejection fraction (< 50%). Of the 59 patients with previous myocardial infarction and abnormal LV ejection fraction, four (7%) were receiving beta blockers and 19 (32%) were receiving calcium channel blockers at the time of admission. CONCLUSIONS: Beta blockers are underutilized, and calcium channel blockers are overutilized in the treatment of older patients with a history of myocardial infarction at the time of admission to a nursing home.

Adrenergic beta-Antagonists↗
PubMed2006

Effects of combination of angiotensin receptor blocker and calcium channel blocker on ox-LDL levels and cardiovascular dysfunction in Dahl rats.

In an effort to assess the cardiovascular benefits of combined angiotensin receptor blockage and calcium channel antagonism, we assessed the chronic effects of the angiotensin type 1 receptor blocker candesartan, the calcium channel blocker benidipine, and the use of a combination therapy in Dahl salt-sensitive (DS) rats. DS rats receiving a high salt diet were treated with either benidipine (4 mg/kg), candesartan (1 mg/kg) or both. Rat blood pressure was measured using a tail-cuff method. Following 12 weeks, the effect on heart weight, plasma-oxidized low-density lipoprotein (ox-LDL) level, endothelium-dependent vasorelaxation, and histology of the heart and aorta was assessed. Blood pressure, heart weight and plasma ox-LDL levels increased, while endothelium-dependent vasorelaxation decreased in the DS rats. Candesartan and benidipine inhibited the increase in blood pressure and heart weight, and the decrease in endothelium-dependent vasorelaxation. The use of benidipine alone or a combination significantly inhibited the increase in ox-LDL levels, whereas candesartan alone had no significant effect on ox-LDL levels. The present findings indicate that, if the monotherapy using ARB could not achieve adequate control of blood pressure, the combination therapy with ARB and benidipine provides the additional reductions in hypertension and cardiac hypertrophy. Moreover, the combination therapy inhibits cardiovascular dysfunction and ox-LDL levels more effectively than use of ARB alone. These results contribute to the possibility of lowering ox-LDL levels as a means of enhancing cardiovascular protection.

Angiotensin II Type 1 Receptor Blockers↗
PubMed1994

Effect of calcium channel blockers on intracellular calcium accumulation.

Protection against acute renal failure by calcium channel blockers include radiocontrast agent, cyclosporin, aminoglycosides, amphotericin B, cisplatin nephrotoxicity, and ischaemia-induced toxicity. Calcium overload occurs in ischaemic cells. The type of calcium channel blocker influences the potential effect on protection against nephrotoxicity. A number of growth factors and hormones induce cellular activation by increasing calcium concentrations. Calcium channel blockers interfere with activation of different cell types, e.g. decrease platelet aggregation, macrophage activation, platelet-activating factor release and also proliferative response of vascular smooth muscle and mesangial cells. Uraemia is also a state of calcium accumulation. Increase of intracellular calcium [Ca2+]i in PMNLs is associated with deactivation. Treatment with calcium channel blockers normalizes elevated PMNL [Ca2+]i and improves functional parameters of PMNLs. Normalization of enhanced [Ca2+]i of PMNLs can also be achieved with effective 1,25(OH)2 vitamin D3 therapy by lowering PTH. Uraemia is also a state of insulin resistance. Elevated levels of [Ca2+]i in insulin target cells diminish sensitivity to insulin at the postbinding site. Therapeutic manoeuvres preventing the increase of cytosolic calcium may improve insulin resistance.

Acute Kidney Injury↗
PubMed1996

Blood pressure and cationic transport systems during combined calcium channel blocker and calcium administration in males.

A double-blind, placebo-controlled parallel study was conducted on the effects of a high daily oral supplementation of 1 g elemental calcium, given twice daily for 16 weeks, followed by additional administration of 2 mg b.i.d. lacidipine or placebo for 8 weeks, on blood pressure, intracellular cationic concentrations and transport systems, plasma total calcium, ionized calcium and calciotropic hormones in normal male subjects. No significant difference in the effect of lacidipine vs. placebo on standing or recumbent systolic or diastolic blood pressure or heart rate was found between calcium- and placebo-treated subjects. The difference in lacidipine effect on erythrocyte Mg2+ concentration and platelet membrane cholesterol content between the placebo and calcium groups was statistically significant. There was no additional effect between groups of lacidipine on erythrocyte and platelet intracellular Ca2+, Na+ and K+ concentrations or transport systems and on plasma Ca2+ levels and calciotropic hormones. Combined calcium and lacidipine administrations in normal male subjects did not induce antihypertensive effects different from those induced by either agent alone.

Administration, Oral↗
PubMed1999

Combination of calcium channel blockers and beta-blockers for patients with exercise-induced angina pectoris: beneficial effect of calcium channel blockers largely determined by their effect on heart rate.

The combination of calcium channel blockers and beta-blockers is more effective for the treatment of exercise-induced angina pectoris than beta-blocker monotherapy. As ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with a negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 mg and 10 mg, diltiazem 200 mg and 300 mg, and mibefradil 50 mg and 100 mg treatment added to baseline beta-blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. All of the calcium channels blockers significantly delayed the onset of 1 mm ST-segment depression on ETT (p < 0.001 for any treatment vs. baseline). In addition, mibefradil, in both low- and high-dose treatments, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 seconds, respectively, p < 0.003 and < 0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 seconds, respectively, p < 0.001 and < 0.001). A stepwise logistic regression analysis revealed that this beneficial effect of calcium channel blockers was largely dependent on their effect on heart rate. Serious symptoms of dizziness likewise occurred significantly more frequently on mibefradil (p < 0.05 vs. diltiazem) and urged no fewer than 19 patients on mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with a negative chronotropic property provide a better delay of ischemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness may reduce this benefit.

Adolescent↗
PubMed1987

Effect of the calcium-channel blockers on calcium accumulation in sarcoplasmic reticulum of skeletal muscle.

Vesicular fragments of sarcoplasmic reticulum isolated from rabbit skeletal muscle were actively loaded with Ca2+ in the presence of ATP and an ATP-regenerating system using Arsenazo III as metallochromic indicator to monitor Ca2+ movements across the membrane. Once the Ca2+ release is triggered by the presence of tetraphenylboron in the reaction medium, the addition of verapamil or diltiazem gives rise to a net Ca2+ entry inside the vesicles. Preincubation in the presence of verapamil does not abolish the tetraphenylboron-induced Ca2+ release, the verapamil-induced Ca2+ accumulation being still observed. There appears to be a high-affinity site for verapamil titrated in the micromolar concentration range, whereas diltiazem demonstrates more complex behavior when its concentration is raised. This study suggests the existence of a Ca2+ pathway (putative channels) which is blocked by the drugs tested allowing Ca2+ accumulation inside the vesicles owing to the Ca2+-dependent ATPase activity.

Adenosine Triphosphate↗
PubMed1994

Early renal graft function in recipients treated with the calcium channel blocker felodipine.

Calcium channel blocking agents (CCB) differ in molecular structure and effects. Each must therefore be evaluated separately. Out of 139 patients who received cadaveric kidney transplants between March 1990 and December 1991 22 were treated with the CCB agent felodipine as antihypertensive therapy on admission and post transplant. The early function of their grafts was compared with that of grafts to patients not treated with any CCB agent pre or post transplant (n = 38). There were no other significant differences in patient or donor characteristics. In the felodipine treated group, 18/22 showed immediate onset of graft function vs 20/38 in the non CCB group (p = 0.02). Dialysis post transplant was required by one felodipine-treated patient vs 12 in the non CCB group. Serum creatinine on day 7 was lower in felodipine treated patients, median 155 vs 259 mumol/l. Felodipine treatment did not seem to cause any significant interaction with cyclosporin A (CyA). The frequency and severity of acute rejection did not differ between the groups.

Adolescent↗
PubMed1996

[Calcium channel blockers in pregnancy].

Calcium channel blockers are used more and more in pregnancy. No teratogenic effect has been observed in humans despite the lack of adequate studies. The use of calcium channel blockers in premature labor and in arterial hypertension may be recommended. In premature labor, maternal tolerance is better than that of beta adrenergic drugs. In hypertensive disorders of pregnancy, current data indicate that calcium channel blockers may be a good second line medication. Acute lowering of maternal blood pressure (by sublingual or intravenous use) may however induce fetal distress.

Antihypertensive Agents↗