Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Calcium Channel Blockers”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1994

The interaction of the calcium channel blockers verapamil and nifedipine with cyclosporin A in pediatric renal transplant patients.

The elimination of cyclosporin A was assessed in eight pediatric renal transplant patients who received calcium channel blockers concomitantly with their immunosuppressive therapy. In three children, verapamil decreased the rate of elimination of cyclosporin A. In five children who received nifedipine, cyclosporin A elimination was also impaired, which contrasts with the reports in adult patients indicating that this calcium channel blocker has no effect on cyclosporin A elimination. When both calcium channel blockers were used on separate occasions in the same patient, nifedipine was less potent than verapamil in depressing cyclosporin A elimination. Although the number of subjects studied is small, these results likely indicate that nifedipine, as well as other calcium channel blocking drugs, must be used with caution in pediatric renal transplant patients.

Adolescent↗
PubMed1988

Species differences in the negative inotropic response of 1,4-dihydropyridine calcium channel blockers in myocardium.

To determine if species differences exist in myocardial response to 1,4-dihydropyridine (DHP) calcium channel blockers, the binding and pharmacologic responses of a series of DHP compounds were examined in both rat and rabbit myocardium. [3H]Nitrendipine was used to label specific binding sites in myocardial membrane particulates. The results of saturation binding experiments (n = 3) indicated no statistically significant difference in either Kd or Bmax between rat and rabbit myocardial membranes (0.19 +/- 0.02 nM and 157 +/- 29 fmol/mg protein in rat and 0.14 +/- 0.06 nM and 227 +/- 125 fmol/mg protein in rabbit). Furthermore, [3H]nitrendipine binding inhibition experiments using 12 unlabeled DHP analogues yielded Ki values for each compound that were almost identical in myocardium from rat and rabbit, resulting in an excellent 1:1 correlation when data for all of the compounds were compared (r = 0.997, p less than 0.001). The negative inotropic effect of five of these DHP compounds was studied in vitro in isolated right papillary muscles from rabbit and right ventricular strips from rat, and concentration required to displace 50% of ligand binding (IC50) values for inhibition of contraction were determined. The IC50 values were significantly greater in rat myocardium than in rabbit myocardium (p less than 0.003). Therefore, a significantly lower potency of DHP calcium channel blockers has been demonstrated in rat compared with rabbit myocardium, and this species difference cannot be explained by a difference in the DHP binding site. Rat myocardium differs from rabbit myocardium in a number of ways that may explain this lower potency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Calcium channel blocker treatment of tumor cells induces alterations in the cytoskeleton, mobility of the integrin alpha IIb beta 3 and tumor-cell-induced platelet aggregation.

Calcium channel blockers of the phenylalkylamine (i.e. verapamil), benzothiazepine (i.e. diltiazem) and dihydropyridine (i.e. nifedipine) classes were evaluated for effects on the tumor cell/platelet interactions using Walker 256 carcinosarcoma cells (W256 cells). When W256 cells were pretreated for 15 min with channel blockers at concentrations of 50-200 microM, macroscopic tumor-cell-induced platelet aggregation was inhibited (order of potency; nifedipine greater than diltiazem much greater than verapamil). However, ultrastructural analysis revealed limited, focal platelet aggregates associated with tumor cell plasma membranes of verapamil- and diltiazem-treated cells. There was no evidence of platelet activation or platelet association with the tumor cell membrane in cells pretreated with nifedipine. Walker 256 cells possess the intergrin alpha IIb beta 3. Tumor cell alpha IIb beta 3 was shown to mediate tumor cell/platelet interactions in vitro [Chopra et al. (1988) Cancer Res. 48:3787]. Patching and capping of surface alpha IIb beta 3 were inhibited by nifedipine greater than diltiazem much greater than verapamil. The degree of inhibition of alpha IIb beta 3 receptor mobility parallels the inhibition of tumor-cell-induced platelet aggregation. W256 cells are characterized by a well-developed microfilament and intermediate filament network and by the absence of a distinct microtubular network. Calcium channel blockers had no effect on the low polymerization level of tubulin. However, they induced rearrangement of microfilament stress fibers. Intermediate filaments were also rearranged but to varying degrees. The order of effectiveness for alteration of intermediate filament organization was nifedipine greater than diltiazem while verapamil was ineffective. We propose that the previously reported inhibition of tumor cell/platelet interaction and tumor cell metastasis by calcium channel blockers [Honn et al. (1984) Clin Exp Metastasis 1:61] is due not only to the effects of the Ca2+ channel blockers on platelets, but also to their effect on the tumor cell cytoskeleton resulting in an inhibition of the mobility and function of the alpha IIb beta 3 receptor.

Animals↗
PubMed2000

The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth.

BACKGROUND/AIMS: To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth. METHOD: A cohort of 135 renal transplant recipients who had been medicated with cyclosporin A in combination with either nifedipine (89) or amlodipine (46) since transplant, took part in the study. The inclusion criteria were that eligible subjects had been in receipt of a kidney transplant for at least 12 months, had at least 10 teeth and had not received specialist periodontal treatment. The age, gender, current drug regimen and dosage were recorded for each participant and alginate impressions taken of both arches. The presence and severity of gingival overgrowth were scored from plaster models. RESULTS: A higher proportion (72%) of the amlodipine group were categorised as having gingival overgrowth compared with only 53% of the nifedipine group, chi square=4.5, p<0.05. Logistic regression analysis was used to explore the relationship between the presence or absence of gingival overgrowth (dependent variable) and age, gender, time since transplant, dose of cyclosporin A, centre in which the patient was treated, and the calcium channel blocker used (independent variables). Independent predictors of gingival overgrowth in this multivariate analysis were whether the individual was treated with amlodipine or nifedipine (p=0.01) and whether the individual was young or old (p=0.01). Within the multivariate analysis, the odds ratio for amlodipine to be associated with gingival overgrowth compared with nifedipine was 3.0 (confidence interval 1.3-6.9). CONCLUSIONS: The prevalence of gingival overgrowth in renal transplant recipients maintained on cyclosporin A and nifedipine is lower than those treated with cyclosporin A and amlodipine.

Adult↗
PubMed2006

Hyperinsulinemia-euglycemia therapy: a useful tool in treating calcium channel blocker poisoning.

Hyperinsulinemia-euglycemia (HIE) therapy, when initiated promptly and aggressively, may offer considerable advantages in the treatment of calcium channel blocker poisoning. Although its mechanism of action is uncertain, HIE improves the efficiency with which the poisoned myocardium uses metabolic fuel, the end result of which is improvements in inotropy and other cardiovascular parameters. Although HIE is not universally accepted, the reports included in the previous issue of Critical Care should prompt clinicians to consider HIE an appropriate therapy specifically for calcium channel blocker poisoning.

Calcium Channel Blockers↗
PubMed2000

Effect of calcium and calcium channel blockers on transient outward current of F76 and D1 neuronal soma membranes in the subesophageal ganglia of Helix aspersa.

Twin-electrode voltage-clamp techniques were used to study the effect of calcium and calcium channel blockers on the transient outward current in isolated F76 and D1 neurones of Helix aspersa subesophageal ganglia in vitro (soma only preparation with no cell processes). On lowering extracellular Ca(2+) concentration from 10 to 2 mm or removing extracellular calcium from the bathing medium, the threshold for this current shifted in a negative direction by 11. 5 and 20 mV, respectively. On the other hand, increasing the extracellular Ca(2+) concentration from 10 to 20 and to 40 mm shifted the steady-state inactivation curves in positive directions on the voltage axis by 7 and 15 mV, respectively. Upon application of calcium channel blockers, Co(2+), La(3+), Ni(2+) and Cd(2+), transient potassium current amplitude was reduced in a voltage-dependent manner, being more effective at voltages close to the threshold. The current was elicited even at a holding potential of -34 mV. The specific calcium channel blockers, amiloride and nifedipine did not shift the activation and steady-state inactivation curves and did not reduce the transient outward current amplitude. It was concluded that the transient outward current is not dependent on intracellular Ca(2+) but that it is modulated by Ca(2+) and di- and trivalent ions extracellularly. The effects of these ions are very unlikely to be due to a surface charge effect because the addition of La(3+) (200 microm) completely reverses the shift in a hyperpolarizing direction when the extracellular Ca(2+) concentration was reduced from 10 to 1 mm and additionally shifts the kinetics further still in a depolarizing direction. The responses seen here are consistent with a specific effect of di- and trivalent ions on the transient outward current channels leading to a modification of gating.

Amiloride↗
PubMed1990

Calcium channel blockers: effect on morphine-induced hypermotility.

Acute morphine treatment has been shown to cause a uniform calcium depletion in various brain regions and to evoke hypermotility in mice. On the other hand, it has been reported previously that calcium channel blockers reduce the behavioral stimulation induced by different methods in mice, and it is known that these drugs increase the morphine analgesia and reduce the abstinence syndrome. The effect of calcium channel blockers, nifedipine and diltiazem, on the morphine- and amphetamine-induced hypermotility were evaluated. Mice activity was measured with photocell motility meters. The results show that neither nifedipine nor diltiazem decrease significantly the motility in control and amphetamine-treated mice; however, when they were administered to morphine-treated mice the hypermotility was significantly reduced. The mechanism responsible for this interference is still unknown.

Animals↗
PubMed1989

Pharmacologic effects of Wy 27569: a combined calcium channel blocker and thromboxane synthetase inhibitor.

Wy 27569 (1,4 dihydro-2-[imidazol-1-yl-methyl]-6-methyl-4- [3-nitrophenyl] pyridine-3,5, dicarboxylic acid 3-ethyl 5-methyl diester) is a combined calcium channel blocker and thromboxane synthetase inhibitor. This article reports the in vivo and in vitro pharmacological studies demonstrating these properties. Wy 27569 evoked rightward shifts and depressed the maximum of calcium dose response curves in potassium depolarised rat aortas [concentration required to inhibit the response by 50% (IC50) = 7.3 nM]. The calcium channel blocker nitrendipine exhibited a similar profile to, although more potent than, Wy 27569 (IC50 = 0.28 nM). Comparison of the data obtained in aortas with the effects of these compounds in electrically stimulated isolated ventricle strips (IC50 for Wy 27569 = 8.3 microM, IC50 for nitrendipine = 0.41 microM) suggests that Wy 27569, like nitrendipine, is a vascular selective calcium channel blocker. Wy 27569 and the thromboxane synthetase inhibitor dazoxiben inhibited the collagen-stimulated production of thromboxane B2 (TXB2, IC50 = 3.9 and 2.8 microM, respectively) and, over the same concentration range, enhanced the production of immunoreactive 6 keto prostaglandin F1 alpha (6 keto-PGF1 alpha) by human platelet rich plasma. Single doses of Wy 27569 (0.3-10 mg kg-1 p.o.) or dazoxiben (3-10 mg kg-1 p.o.) evoked a dose-related reduction of TXB2 and enhancement of immunoreactive 6 keto PGF1 alpha levels in rat plasma and serum. Nitrendipine (0.3-10 mg kg-1 p.o.) had no significant effect on either eicosanoid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of calcium channel blockers and hydralazine on epinephrine-induced stimulation of glucose output from primary cultured rat hepatocytes.

Effects of calcium channel blockers from structurally different classes and hydralazine on epinephrine-induced stimulation of glucose output from primary cultured rat hepatocytes were examined in vitro. Diltiazem, verapamil, and nifedipine dose-dependently inhibited the epinephrine-induced stimulation of glucose output from the primary cultured rat hepatocytes. In contrast to these agents, nicardipine caused decreases in the basal and epinephrine-stimulated glucose output from rat hepatocytes in primary culture. Hydralazine treatment was found to reduce the response in a dose-dependent manner. These results indicate that the calcium channel blockers and hydralazine did not potentiate but reduce the epinephrine-induced stimulation of glucose output from primary cultures of rat hepatocytes in vitro.

Animals↗
PubMedDate not supplied

Comparative acute effects of the calcium channel blockers tiapamil, nisoldipine, and nifedipine on blood pressure and some regulatory factors in normal and hypertensive subjects.

To clarify the pharmacological profile of the two new calcium channel blockers tiapamil and nisoldipine in humans, their acute effects as compared with those of the reference agent nifedipine were assessed in 10 normal subjects and 10 patients with essential hypertension. Blood pressure (BP), heart rate (HR), plasma and urinary catecholamine, sodium and potassium, plasma renin and aldosterone levels, and urinary prostaglandin E2 and F2 excretion rates were determined before and up to 4 or 5 h (urine values) after intravenous injection of placebo (20 ml 0.9% NaCl), tiapamil 1 mg/kg body weight, nisoldipine 6 micrograms/kg, or nifedipine 15 micrograms/kg. The four studies were performed at weekly intervals according to Latin square design. All three calcium channel blockers significantly (p less than 0.05 or lower) lowered BP and distinctly increased sodium excretion in hypertensive patients, but had only little influence on these parameters in normal subjects. HR was increased in both groups. Changes in BP and HR were maximal at 5 min and largely dissipated 3 h after drug injection. Effects on BP and HR, as well as concomitant mild increases in plasma norepinephrine and renin levels that occurred in both groups, tended to be more pronounced (about double) following nisoldipine than following tiapamil or nifedipine at the dosages given. Plasma aldosterone, epinephrine levels, and prostaglandin excretion rates were not consistently modified. These findings demonstrate that tiapamil and nisoldipine possess distinct antihypertensive properties in humans. Different chronotropic and renin-activating effects of different calcium channel blockers may be determined, at least in part, by a different influence on sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Effects of two calcium channel blockers on messenger RNA expression of endothelin-1 and nitric oxide synthase in cardiovascular tissue of hypertensive rats.

OBJECTIVE: The aim of this study was to investigate the effects of calcium channel blockers on messenger RNA expression of endothelin-1 and endothelial-type nitric oxide synthase in the cardiovascular tissue of stroke-prone spontaneously hypertensive rats (SHRSP). MATERIALS AND METHODS: The calcium channel blocker nilvadipine (1.0 or 3.2 mg/kg per day) was subcutaneously administered to two groups of SHRSP, from 4 or 8 weeks of age, for 8 weeks and 4 weeks, respectively. For comparison, nifedipine (3.2 mg/kg per day) was similarly administered to SHRSP from 4 weeks of age for 8 weeks. Kidney, heart, aorta and brain tissue samples were obtained when the rats were 12 weeks old. Messenger RNA expression of endothelin-1 and endothelial-type nitric oxide synthase was determined by reverse transcription-polymerase chain reaction followed by Southern blotting and a ribonuclease protection assay, respectively. Results were compared with those in untreated SHRSP and Wistar-Kyoto rats at 12 weeks of age. RESULTS: Both nilvadipine and nifedipine significantly decreased blood pressure in SHRSP. Although there were no changes in the weights of the kidney and brain, there was a significant decrease in the weight of the left ventricle of the groups treated with nilvadipine (1.0 mg/kg per day: mean +/- SEM 0.282 +/- 0.003 g; 3.2 mg/kg per day: 0.269 +/- 0.005 g) and nifedipine (1 mg/kg/day: 0.281 +/- 0.012 g) for 8 weeks compared with untreated SHRSP (0.301 +/- 0.004 g). Endothelin-1 messenger RNA expression, which was significantly increased by about twofold in the kidney, heart and brain of SHRSP compared with Wistar-Kyoto rats, was normalized by both calcium blockers. Endothelin-1 messenger RNA expression, which was decreased in the aorta of SHRSP, was further decreased by both calcium blockers. While there was no significant difference in endothelial-type nitric oxide synthase messenger RNA expression in the kidney, heart and aorta between the untreated SHRSP and Wistar-Kyoto rats, expression in the aorta was significantly increased in the group treated with these calcium blockers for 8 weeks from 4 weeks of age. CONCLUSIONS: These results suggest that, in addition to their potent antihypertensive effects, calcium channel blockers may exhibit cardiovasculoprotective and renoprotective effects by modifying mRNA expression of endothelin-1 and endothelial-type nitric oxide synthase in tissue.

Animals↗
PubMed1997

The calcium channel blocker controversy in perspective.

Periodically in the history of hypertensive therapy there have been minor storms that have significantly affected the utilization of entire classes of agents. The first storm struck with the case-control studies suggesting that reserpine was associated with an increased risk of carcinoma of the breast, a claim subsequently disproved by a number of other studies. The second storm was initiated by a subanalysis of the Multiple Risk Factor Intervention Trial (MRFIT), from which it was inferred that, in a subset of hypertensive patients, diuretic treatment may have been harmful rather than beneficial. Despite this claim and other speculations, diuretics-especially at low doses-remain a gold standard of antihypertensive therapy. Recently, a third storm has developed in the field of antihypertensive therapy: a case-control study report and a non-randomized cohort study have questioned the use of calcium channel blockers in hypertension. The case-control study suffers from the limitations inherent in this study design, which often gives rise to conflicts and contradiction. In fact, another case-control study published in 1995 reached exactly the opposite conclusions and claimed that calcium channel blockers were associated with significantly less myocardial infarction than traditional antihypertensive therapy. A meta-analysis was also presented as supporting the non-randomized studies questioning the safety of calcium channel blockers. However, it refers to patients with coronary heart disease, not to patients with hypertension, and also combined studies performed with different aims, and data from short-term and long-term studies using short-acting formulations of calcium channel blockers. The controversies generated by these reports have gone well beyond their scientific merit. For final judgement we should wait for well-designed prospective studies, several of which are under way. For the time being, there is no reason to change the current practice of antihypertensive therapy, as summarized in the recommendations of both the United States Joint National Committee and the World Health Organization/International Society of Hypertension Committee, that is, diuretics and beta-blockers are among those antihypertensive agents with clearly proven benefits in mortality-morbidity studies, but calcium channel blockers as well as ACE inhibitors and alpha-blockers can also be used profitably in the treatment of hypertension.

Adrenergic beta-Antagonists↗
PubMed1995

Calcium channel blockers as inhibitors of angiotensin I-converting enzyme.

Using ion-exchange chromatography of dialyzed human urine from healthy and hypertensive patients, we detected two peaks of angiotensin I-converting enzyme (ACE) activity on hippuryl-His-Leu eluted at ionic strengths of 0.7 (F1 peak) and 1.25 (F2 peak) mS. These hydrolytic activities decreased gradually in the urine of patients submitted to isradipine treatment, F2 and F1 disappearing after 12 and 24 hours, respectively. By Western blot analysis, the urine fractions corresponding to both peaks from healthy and untreated patients presenting ACE activity and from treated patients (24 hours) without this activity were recognized by an ACE-specific antibody. These results indicated that ACE was present but inhibited in the urine of isradipine-treated patients. In vitro assays with ACE isolated from human urine and guinea pig plasma demonstrated that the enzyme is inhibited by isradipine and other commercially available calcium channel blockers, such as felodipine, nifedipine, and verapamil. A noncompetitive inhibition was observed with all calcium channel blockers studied. In conclusion, these results suggest that besides the primary effect on calcium channels, the more commonly used calcium channel blockers are also ACE inhibitors. The development of efficient calcium channel blockers with higher ACE inhibitory activity could result in interesting bifunctional antihypertensive drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Failure of calcium channel blockers to improve ventricular relaxation in humans.

OBJECTIVES: The objective of this study was to ascertain whether the reversal of low peak filling rates after administration of calcium channel blockers in patients with diastolic dysfunction indicates true improvement in the rate of ventricular relaxation and left ventricular end-diastolic pressure measured by invasive indexes. BACKGROUND: Depressed filling rates measured noninvasively have been associated with diastolic dysfunction, specifically abnormal relaxation of the left ventricle. There is a reversal of these low peak filling rates after administration of calcium channel blockers. METHODS: Doppler echocardiographic measurements of peak filling rates were made and invasive high fidelity manometer-tipped pressures were measured before and after administration of verapamil (0.1 mg/kg body weight) in 20 patients with coronary artery disease who had an ejection fraction > 40% and decreased peak filling rates. RESULTS: Verapamil caused significant increases in the peak filling rate, as measured by early transmitral (E) flow velocity, from 0.57 +/- 0.16 m/s to 0.77 +/- 0.15 m/s (p < 0.01), indicating reversal of decreased peak filling rates. Concomitantly, left ventricular end-diastolic pressure increased from 18.0 +/- 7.7 mm Hg to 24.1 +/- 9.0 mm Hg (p < 0.001). The time constant of relaxation was variable, with an overall significant increase from 45.8 +/- 10.4 ms to 53.2 +/- 14.6 ms (p = 0.01). CONCLUSIONS: Verapamil administered intravenously produced reversal of decreased peak filling rates in patients with coronary artery disease and normal ventricular function. However, there was an increase in left ventricular end-diastolic pressure as well as an overall prolongation of the time constant of relaxation. Therefore, changes in peak filling rates do not accurately reflect the response of ventricular relaxation to drug interactions. Thus, calcium channel blockers should be used cautiously in the empiric treatment of patients with diastolic dysfunction.

Aged↗
PubMed2002

Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy.

UNLABELLED: OBJECTIVES; We present a meta-analysis based on three recent, substantial, randomized outcome trials and several smaller trials that compared calcium channel blockers (CCBs) with conventional therapy (diuretics or beta-blockers) or with angiotensin-converting enzyme (ACE) inhibitors. BACKGROUND: There is continuing uncertainty about the safety and efficacy of CCBs in the treatment of hypertension. Previous meta-analyses conflict and suggest that CCBs increase myocardial infarction (MI) or protect from stroke. METHODS: Standard procedures for meta-analysis were used to analyze three major trials on 21,611 patients and another three lesser studies to a total of 24,322 patients. RESULTS: Calcium channel blockers have a strikingly similar risk of total and cardiovascular mortality and of major cardiovascular events to conventional therapy. Calcium channel blockers give a lower risk of nonfatal stroke (-25%, p = 0.001) and a higher risk of total MI (18%, p = 0.013), chiefly nonfatal (18%). After performing the Bonferroni correction for multiplicity, these p values become 0.004 and 0.052, respectively. When compared with ACE inhibitors in 1,318 diabetic patients, CCBs had a substantially higher risk of nonfatal (relative risk [RR] = 2.259) and total MI (RR = 2.204, confidence interval 1.501 to 3.238; p = 0.001 or 0.004 with Bonferroni correction). Total and cardiovascular mortality rates are similar. To confirm the hypothesis that ACE inhibitors are superior to CCBs in diabetic patients requires more trial data, especially with renal end points. CONCLUSIONS: Mortality (total and cardiovascular) and major cardiovascular events with CCBs were apparently similar to those events seen with conventional first-line therapy (diuretics or beta-blockers). Stroke reduction more than balanced increased MI. In diabetics, CCBs may be less safe than ACE inhibitors.

Adrenergic beta-Antagonists↗
PubMed1994

Effect of calcium channel blockers on the growth of human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses.

Vascular restenosis after invasive interventions is an important clinical problem for which no preventive pharmacologic therapy exists. Calcium channel blockers have been shown to inhibit myointimal hyperplasia in animal models of restenosis and in some small and flawed clinical coronary restenosis trials. We examined the inhibitory effect of amlodipine, verapamil, and diltiazem on the growth of cultured human vascular smooth muscle cells (VSMC) derived from saphenous vein (n = 20) and graft stenoses (n = 7), in 14-day proliferation assays and [methyl 3H]thymidine uptake studies. Amlodipine and verapamil produced significant inhibition (30%) of VSMC proliferation and DNA synthesis at 10 microM but not at 500 nM-1 microM. To our knowledge, this is the first study to examine the antiproliferative effect of calcium channel blockers in VSMC derived from human graft stenoses. Growth inhibition of VSMC from graft stenoses was not significantly different from that of control saphenous vein-derived cells. We conclude, therefore, that calcium channel blockers inhibit human VSMC proliferation in vitro, regardless of whether the cells were grown from graft stenoses or saphenous vein. However, the concentrations at which these calcium channel blockers elicit antiproliferative effects may not be attainable during therapeutic dosing in humans.

Amlodipine↗
PubMed2005

The N- and L-type calcium channel blocker cilnidipine suppresses renal injury in dahl rats fed a high-sucrose diet, an experimental model of metabolic syndrome.

BACKGROUND/AIMS: The L/N-type calcium channel blocker (CCB) cilnidipine has been demonstrated to suppress progressive renal disease in a variety of experimental models, but the characteristic effects of N-type calcium channel blocking action on renal injury have not been examined in detail. Therefore, we investigated the beneficial effects of cilnidipine on renal injury in Dahl salt-sensitive (Dahl S) rats fed a high-sucrose diet (HSD), which mimics metabolic syndrome, and compared them with the effects of an L-type CCB, amlodipine. METHODS: Male Dahl S rats were divided into groups with similar blood pressure at 8 weeks of age and fed an HSD. They received vehicle, cilnidipine or amlodipine for 27 weeks. At 35 weeks of age, urine and blood samples were collected for physiological analysis, and the kidneys were removed for histopathological evaluation. RESULTS: Cilnidipine reduced albuminuria, glomerular hypertrophy, glomerular expression of ICAM-1, ED-1-positive cell infiltration and interstitial fibrosis compared with vehicle-treated rats. In contrast, amlodipine had no effect on these parameters. Urinary norepinephrine excretion, renal expression of renin mRNA and renal tissue levels of angiotensin II were increased only in the amlodipine-treated group. CONCLUSION: Cilnidipine provided superior protection against renal damage compared with amlodipine in Dahl S rats given an HSD. The different effects between these two drugs may be partly explained by their different actions on the renal sympathetic nerve activity and the renin-angiotensin system through the N-type calcium channel blocking action.

Amlodipine↗
PubMed2001

The influence of transforming growth factor-beta1 gene polymorphisms on the severity of gingival overgrowth associated with concomitant use of cyclosporin A and a calcium channel blocker.

BACKGROUND: The purpose of this study was to determine whether the prevalence and severity of gingival overgrowth in renal transplant recipients concomitantly treated with cyclosporin and a calcium channel blocker was associated with functional polymorphisms within the signal sequence of the transforming growth factor-(TGF)beta1 gene. METHODS: The extent and severity of gingival overgrowth for 164 renal transplant recipients immunosuppressed with cyclosporin A and concomitantly taking a calcium channel blocker since transplant were entered into the study (86 in Manchester, 78 in Belfast). Two biallelic polymorphisms of the TGF-beta1 gene were studied at position +869, codon 10 (leucine to proline substitution), and position +915, codon 25 (arginine to proline substitution). RESULTS: Subjects who were homozygous for proline at codon 10 had significantly higher overgrowth scores than those who were heterozygous (P= 0.03) or homozygous for leucine (P= 0.01). Subjects who were heterozygous (arginine/proline) at codon 25 had a significantly higher (P= 0.04) gingival overgrowth score than those who were homozygous for arginine. Logistic regression analysis indicated that for codon 25 independent predictors of severe gingival overgrowth were the heterozygous arginine/proline genotype (P= 0.009) and whether the individual was young (P= 0.05). CONCLUSIONS: Polymorphisms in the TGF-beta1 gene influence the expression of gingival overgrowth in renal transplant recipients concomitantly treated with cyclosporin and a calcium channel blocker. The polymorphism in the TGF-beta1 gene at codon 25 represented an independent genetic determinant of severe gingival overgrowth in the susceptible subjects studied.

Adult↗