Role Of Calcium Channel Blockers Research Articles

L-type calcium channel blockade alleviates molecular and reversal spatial learning and memory alterations induced by entorhinal amyloid pathology in rats

The entorhinal cortex (EC) is one of the most vulnerable brain regions that is affected by beta amyloid (Aβ) in the early phases of Alzheimer's disease (AD). Calcium dyshomeostasis is one reason of Aβ pathology and the role of calcium channel blockers (CCBs) in this phenomenon has not fully understood. In this study, we investigated the possible neuroprotective effect of CCBs, nimodipine and isradipine against amyloid pathogenesis in EC. The Aβ 1-42 was injected bilaterally into the EC of male rats and spatial performance was assessed between 7 and 12 days after Aβ injection by Morris water maze test. Animals were daily treated by injection of various doses of nimodipine or isradipine (both at 3, 10, or 30μg/2μl) or their vehicles into the lateral ventricle until the start of behavioral test. Lesion in EC was assessed by measuring some proteinases involved in calcium dependent apoptotic pathway (calpain 2, caspase 12 and 3). Despite normal performance in probe test, Aβ treated rats showed delayed acquisition in a spatial reference memory task. Aβ treated rats revealed delayed acquisition in reversal memory and had deficit in probe test. The observed impairments were attenuated by isradipine (10 and 30μg but not 3μg) and nimodipine (30μg). Calpain 2, caspase 12 and 3 were increased in the Aβ treated animals which was partially antagonized by isradipine and nimodipine. It is concluded that CCBs might have beneficial therapeutic effects in AD especially in the early phases of this disease.

Calcium Antagonist Added to Angiotensin Receptor Blocker: A Recipe for Reducing Blood Pressure Variability?

See related article, pp 1132–1138 The results of a number of studies performed over the years support the hypothesis that short-term blood pressure (BP) variability (BPV) assessed within 24 hours is an independent determinant of organ damage and cardiovascular events in hypertension.1,2 More recently, a few articles have raised interest also in BP fluctuations occurring over longer time periods. Rothwell et al3 assessed the variability in clinic BP or in average 24-hour ambulatory BP values occurring between visits. They analyzed previously collected data demonstrating an independent association of such visit-to-visit variability with (mainly) cerebrovascular events. The principal disadvantage of this approach, however, is its limited applicability in the daily management of hypertensive patients, where it is difficult to obtain BP data under a stable antihypertensive treatment regimen over a consistent number of visits. An alternative method, devoid of this difficulty, is to assess day-by-day BPV making use of home BP values obtained over several days. Its validity is supported by studies demonstrating the relationship of day-by-day BPV with cardiovascular outcomes.4 However, in spite of the data supporting the clinical relevance of BP fluctuations over time, a number of reasons have until now prevented the introduction of BPV assessment in daily clinical management of hypertension. Among them is the yet missing direct evidence in humans that a reduction in BPV by treatment provides cardiovascular protection beyond that offered by BP lowering. Moreover, although animal studies suggested the possible beneficial role of calcium channel blockers (CCBs) in lowering BPV independent of mean BP reduction,5 longitudinal data in humans on the ability of antihypertensive drugs to reduce BPV independently from their effect on mean BP levels are still largely missing. A …

Systemic sclerosis and the heart

When present clinically, cardiac involvement in systemic sclerosis (SSc) is a major risk factor for death. It is therefore vitally important to understand the epidemiology, screening, diagnosis, and treatment of the cardiac manifestations of SSc. The epidemiology of cardiac involvement in SSc has been the subject of several recent studies. Most importantly, the prevalence of overt left ventricular (LV) systolic dysfunction and its associated risk factors have been defined, and patients with diffuse cutaneous SSc appear to be most susceptible to direct cardiac involvement. From a diagnostic and screening standpoint, tissue Doppler echocardiography and natriuretic peptides have provided fresh insight into subclinical cardiac dysfunction in SSc. Newer techniques, such as speckle-tracking echocardiography, diffuse myocardial fibrosis imaging, and absolute myocardial perfusion imaging, are poised to further advance our knowledge. Lastly, there is now consistent observational data to suggest a central role for calcium channel blockers in the treatment of microvascular ischemia and prevention of overt LV systolic dysfunction, although randomized controlled trials are lacking. Recent studies have improved our understanding of cardiac involvement in SSc. Nevertheless, key questions regarding screening, diagnosis, and treatment remain. Novel diagnostic techniques and multicenter studies should yield important new data, which will hopefully ultimately result in improved outcomes.

The role of calcium channel blockers and resveratrol in the prevention of paraquat-induced parkinsonism in Drosophila melanogaster: a locomotor analysis

Studies have suggested that neuronal loss in Parkinson's disease (PD) could be related to the pacemaker activity of the substantia nigra pars compacta generated by L-type Ca(v) 1.3 calcium channels, which progressively substitute voltage-dependent sodium channels in this region during aging. Besides this mechanism, which leads to increases in intracellular calcium, other factors are also known to play a role in dopaminergic cell death due to overproduction of reactive oxygen species. Thus, dihydropyridines, a class of calcium channel blockers, and resveratrol, a polyphenol that presents antioxidant properties, may represent therapeutic alternatives for the prevention of PD. In the present study, we tested the effects of the dihydropyridines, isradipine, nifedipine, and nimodipine and of resveratrol upon locomotor behavior in Drosophila melanogaster. As previously described, paraquat induced parkinsonian-like motor deficits. Moreover, none of the drugs tested were able to prevent the motor deficits produced by paraquat. Additionally, isradipine, nifedipine, resveratrol, and ethanol (vehicle), when used in isolation, induced motor deficits in flies. This study is the first demonstration that dyhidropyridines and resveratrol are unable to reverse the locomotor impairments induced by paraquat in Drosophila melanogaster.

Prescribing calcium channel blockers

This paper examines the role of calcium channel blockers (CCBs) and the various modes of action of each of the sub-types of CCBs. CCBs can be prescribed in a variety of cardiovascular disorders, and the selectivity of each type of CCB will be discussed.

Welcome to “Ion Channels: Key Therapeutic Targets”

Welcome to “Ion Channels: Key Therapeutic Targets”

The role of calcium channel blockers, steroids, anticoagulation, antiplatelet drugs, and endothelin receptor antagonists

The rationale for the drug therapy of pulmonary artery hypertension is to reduce mortality and morbidity caused by failure of right ventricular adaptation to an elevated pulmonary vascular resistance. We review the evidence for the use of calcium-channel blockers, steroids, anticoagulation, antiplatelet drugs, and endothelin receptor antagonists in the management of pulmonary artery hypertension. The drugs we discuss are more suited to long-term outpatient therapy. These drugs have not found a routine place in intensive care management, and calcium-channel blockers are contraindicated in patients with right-heart failure. The efficacy of many agents has been extrapolated from data acquired in adult patients and applied to children. All of us involved in the care of young patients with pulmonary artery hypertension should advocate for both the inclusion of younger patients in clinical trials and the design of distinctly pediatric trials with pharmaceutical and drug administration agencies. It is only with data derived from pediatric inclusive studies that we shall be able to recommend therapy with strong evidence. However, it is important to point out that the use of newer agents for the treatment of chronic pulmonary artery hypertension (prostacyclin, endothelin receptor antagonists, nitric oxide, and sildenafil) have not been shown to improve survival unequivocally and have relied on surrogates, such as exercise capacity. There are no long-term studies of survival benefit. Recent studies have included data on time to clinical worsening, which may be a more predictive surrogate of survival.

A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention

Stroke is a leading cause of death and disability worldwide. The importance of lowering blood pressure for reducing the risk of stroke is well established. However, not all the benefits of antihypertensive treatments in stroke can be accounted for by reductions in BP and there may be differences between antihypertensive classes as to which provides optimal protection. Dihydropyridine calcium channel blockers, such as amlodipine, and angiotensin receptor blockers, such as valsartan, represent the two antihypertensive drug classes with the strongest supportive data for the prevention of stroke. Therefore, when combination therapy is required, a combination of these two antihypertensive classes represents a logical approach.

The effect of oral verapamil on the visual evoked potentials in multiple sclerosis patients.

Ionic channel rearrangements through demyelinated axons or supporting media play a significant role in remission of neurological deficits in multiple sclerosis (MS) patients. The role of calcium channel blockers on the MS demyelination sequels is controversial. We studied the change of visual evoked potential (VEP) P100 induced by verapamil in MS patients. We conducted a randomized double blind, placebo controlled, clinical trial on two groups of 20 clinically definite MS patients who had no relapse during the previous one year. Changes in P100 latency were compared between subjects taking 3 dosages of oral verapamil 40 mg, every 8 hours and subjects taking placebo. In the verapamil group, the P100 latencies shortened an average of 6.1 +/- 4 ms compare to placebo group 1 +/- 0.5 ms (P<0.05). Verapamil had no significant effect on the VEP duration. The present study suggests pharmacological manipulation of calcium-dependent process, possibly at the level of demyelinated axon, can rapidly facilitate conduction of electrical impulses in visual pathways of stable MS patients.

Role of calcium channel blockers in preventing heart failure in hypertensive and coronary artery disease patients

Role of calcium channel blockers in preventing heart failure in hypertensive and coronary artery disease patients

Aggressive blood pressure control and stroke prevention: role of calcium channel blockers

Cerebrovascular disease is a major cause of morbidity and mortality worldwide and its prevalence is expected to increase as a result of projected demographic trends. Stroke is one of the leading causes of disability and death of over 30 million people each year worldwide. Hypertension is the most important modifiable risk factor for stroke. Recent data indicate that treatment with antihypertensive drugs reduces the incidence of all strokes in men (by 34%), women (by 38%), the elderly (by 36%), including those older than 80 years (by 34%), younger persons, those with systolic and diastolic hypertension, persons with isolated systolic hypertension, and those with a history of stroke or transient ischemic attack (by 28%). Furthermore, several large, prospective, randomized, clinical outcome trials have shown that calcium channel blockers (CCBs) are effective and safe antihypertensive drugs compared with placebo and reduce the cardiovascular morbidity and mortality of treated patients. Moreover, when CCBs were compared with conventional antihypertensive drugs they demonstrated similar blood pressure-lowering effects and similar reductions in cardiovascular morbidity and mortality, with the exception of a higher incidence of heart failure and fatal myocardial infarction in some studies. Considering all the evidence available today, however, these drugs should be considered safe for the treatment of the uncomplicated hypertensive patient in combination with other drugs. They can also be used as first-line therapy for older, stroke-prone hypertensive patients. The aim of this review is to summarize the role of CCBs in the prevention of stroke.

Adrenalectomy potentiates the anti-inflammatory activity of a calcium channel blocker

Calcium movement is important in the activation of inflammatory cells. Prior studies have shown that calcium channel blockers (CCBs) inhibit carrageenan-induced paw edema in rats by acting at pituitary and hypothalamic levels. Here we evaluated the role of calcium channel blockers and their regulation via the hypothalamus-pituitary-adrenal (HPA) axis in acute and chronic models of rat paw inflammation, using both carrageenan (acute) and formalin (chronic) as inflammation inducers. Adrenalectomized (ADX) and intact Sprague Dawley rats (n = 4 per group) weighing 150-250 each were treated with an intraperitoneal injection of nifedipine (400 microg/kg) or vehicle. Edema was assessed plethysmometrically by evaluating paw volume changes. The results show a significant contradiction between acute and chronic inflammation data. In intact animals, nifedipine demonstrated a significant anti-inflammatory effect in the acute inflammatory model but not in the chronic model. In adrenal-ectomized animals, the anti-inflammatory effect of nifedipine was significantly enhanced both in acute and chronic models. We conclude that adrenalectomy plays a significant role in modulating the inflammatory pathway in the presence of calcium channel blockers.

Dual Therapy in Hypertensive Patients with Coronary Artery Disease: The Role of Calcium Channel Blockers and ??-Blockers

The majority of hypertensive patients require combination therapy to achieve BP goals. Guidelines recommend dual therapy in newly diagnosed patients with BP > 160/100mm Hg. Calcium channel blocker (CCB)/ACE inhibitor and beta-blocker (beta-adrenoceptor antagonists)/diuretic combinations are among regimens considered effective for BP control. ACE inhibitors, beta-blockers, and CCBs are recommended for use in patients after myocardial infarction (MI). Statistical modeling from INVEST (INternational VErapamil-Trandolapril STudy), suggests an association between dual and triple therapy and decreased risk of primary outcome ([PO] first occurrence of death, nonfatal MI, or nonfatal stroke) in patients with hypertension and coronary artery disease (CAD). This study explores the utility of dual antihypertensive therapy by reporting BP and cardiovascular outcomes for INVEST patients who predominantly received either a CCB/ACE inhibitor or a beta-blocker/ diuretic regimen. 1170 patients were selected for analysis. After 24 months of treatment, BP control (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI criteria) was 82.1% and 82.6% in the verapamil sustained release (SR) + trandolapril (Ve + Tr) and atenolol + hydrochlorothiazide (At + HCTZ) groups, respectively (p = 0.86). In Ve + Tr compared to At + HCTZ patients, adjusted risk for PO (hazard ratio [HR] 0.63; 95% CI 0.37, 1.05; p = 0.07) and unadjusted risks for secondary outcomes including death (HR 0.70; 95% CI 0.40, 1.25), total MI (HR 0.82; 95% CI 0.35, 1.90), total stroke (HR 0.81; 95% CI 0.25, 2.65) and new diabetes (HR 0.88; 95% CI 0.55, 1.41) were not statistically different. This analysis shows that combination treatment with either Ve+ Tr or At +- HCTZ is effective in achieving BP control and produces similar outcomes in hypertensive patients with CAD.

Calcium channel blockers in the spectrum of antihypertensive agents

Calcium channel blockers (CCBs) are widely used in the treatment of hypertension. Through blood pressure reduction, and possibly other mechanisms such as antioxidative effects, they may play a role in diminishing the risk for a variety of cardiovascular outcomes. The combination of CCBs with other newer antihypertensive agents such, as ACE inhibitors and angiotensin receptor blockers, may provide complementary effects on risk reduction in cardiovascular adverse events and renal disease. Although the efficacy of CCBs as antihypertensive agents has been adequately demonstrated, there have been concerns regarding the use of short acting dihydropyridines after acute myocardial infarction. There have also been questions about the role of CCBs with regards to other antihypertensive agents in renal disease. For example, differential effects of dihydropyridine and non-dihydropyridine CCBs may affect progression of renal disease and risk for diabetes. Certain precautions involving drug interactions are needed because of the effects of CCBs on the CYP450 enzyme systems.

Use of calcium channel blockers after stroke is not associated with poor outcome

Control of hypertension is essential for the secondary prevention of stroke. Although several trials have assessed the role of calcium channel blockers (CCBs) in the acute stroke, few address their safety and efficacy in secondary prevention. The recovery process after stroke requires neurite outgrowth, which may be dependent on activation of calcium channels and NMDA receptors. We asked whether treatment of hypertension using CCBs is safe during the recovery of patients following stroke and whether it contributes to their functional outcome. The Registry of the Canadian Stroke Network provided access to information from 1545 patients with ischemic stroke. Primary outcome variables were mortality and functional outcome, which was assessed using the Stroke Impact Scale-16. Patients discharged on CCB had a 2.5% 6-month mortality rate compared with 5.5% in those who were not on CCB at discharge (OR 0.38, 95% CI 0.17-0.88). There was no change in 6-month mortality with respect to treatment with ACE-I, B-blockers or diuretics at discharge. Patients that were admitted on CCB had improved SIS-16 at 6-months if they were also discharged on CCB, as compared with patients who had their CCB discontinued (73.8 veas 66.8, p = 0.032). CCB treatment at the time of discharge did not impede functional recovery, and was associated with reduced mortality and improved SIS-16 at 6 months.

ROLE OF VERAPAMIL (CALCIUM CHANNEL BLOCKER) AND LISINOPRIL (ANGIOTENSIN CONVERTING ENZYME INHIBITOR) ON MYOCARDIAL TOLERANCE TO ACUTE ISCHAEMIA

This work aims to clarify the role of calcium channel blocker (verapamil) and angiotensin-converting enzyme inhibitor (lisinopril) on myocardial is-chaemia reperfusion injury. The study was done using isolated rabbits hearts and Langendroffs apparatus for recording myocardial contractility, heart rate and coronary flow, also glu­cose uptake by coronary slices was estimated by glucose enzymatic kit. The work included 4 groups; Group A to study effect of ischaemia and re­perfusion on mentioned parameters, Group B to study effect of verapamil and lisinopril on tested parameters, Group C to study the effect of 5 minutes preischaemia administration of verapamil and lisinopril on tested pa­rameters and Group D to study the ef­fects of administration of verapamil and lisinopril with reperfusion on pa­rameters mentioned before. Results concluded that global ischaemia de­creased the myocardial contractility and heart rate but increases glucose uptake, verapamil is a potent drug used to decrease myocardial contrac­tility, heart rate and increase coronary flow in ischaemic hearts. Lisinopril is a drug of choice to improve contractil­ity and heart rate when administered preischaemic or with reperfusion.

The Role of Dihydropyridine Calcium Channel Blockers in the Treatment of Hypertension and Cardiovascular Disease – An Update

Recent evidence supports a central role for calcium channel blockers (CCBs), and in particular the dihydropyridine (DHP) agents, in the treatment of hypertension and cardiovascular disease (CVD). We review here the findings of recent trials, systematic reviews and meta-analyses that rebut those of the single, yet widely-publicised, earlier unfavourable meta-analysis.

Management of Hypertensive Chronic Kidney Disease: Role of Calcium Channel Blockers

Both the prevalence and incidence of end-stage renal disease have been increasing in the United States over the past two decades. Diabetes and hypertension are the attributable causes for more than three fourths of all new cases of end-stage renal disease. The overwhelming majority of diabetics with nephropathy are hypertensive, and lowering blood pressure is indicated in all patients with chronic kidney disease because of the increased risk for cardiovascular morbidity and mortality. Multiple studies indicate that reaching goal systolic blood pressure in patients with chronic kidney disease generally requires three to four antihypertensive agents. A number of medication combinations can effectively reduce blood pressure in the chronic kidney disease patient. In this regard, adding a calcium channel blocker to an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker helps in reaching goal blood pressure while preserving renal function in both diabetics and nondiabetics with proteinuria.

The role of calcium channel blockers in the treatment of diabetic nephropathy

Diabetic nephropathy (DNP) is a chronic renal disease (CRD) and a major cause of illness and premature death in peoplewith diabetes mellitus (DM). It is the single most important cause of end-stage renal disease in the Western world andaccounts for more than a quarter of all end-stage renal diseases. This article reviews the current development in DNP and thetherapeutic challenge with particular reference to the role of calcium channel blockers. Moreover, renal ischaemia hastens theprogression of DNP. Diltiazem and amlodipine have a tendency to reverse the changed parameters toward normal values butdo not affect the biochemical parameters. Generally speaking, diltiazem is better than amlodipine in reversing biochemicaland histopathological changes produced by DNP, and captopril reverses most of the changed parameters with the exceptionof the histopathological changes. These agents have nephroprotective properties and delay the progression of DNP.

Calcium Channel Blockade and Preservation of Renal Graft Function in Cyclosporine-Treated Recipients: A Prospective Randomized Placebo-Controlled 2-Year Study

Studies have provided conflicting results as to the protective role of calcium channel blockers (CCB) in cyclosporine-treated patients with regard to blood pressure control and preservation of renal graft function. Lacidipine is a dihydropyridine CCB that possesses antioxidative, anti-atherosclerotic, and anti-adhesion properties and was shown to prevent cyclosporine-induced nephrotoxicity in a rat model. We conducted a multicenter prospective, randomized, placebo-controlled study in 131 de novo recipients of a cadaveric renal allograft on cyclosporine therapy. The aim of this 2-year study was to assess the effects of lacidipine on graft function (plasma iohexol clearance), renal plasma flow, anastomotic arterial blood flow, deterioration of renal function, blood pressure, acute rejection, and hospitalization rate. A total of 118 recipients were available for intention-to-treat analysis on efficacy (lacidipine: n=59; placebo: n=59). Graft function assessed by serum creatinine concentration and glomerular filtration rate measured as plasma iohexol clearance, was persistently better in lacidipine-treated patients from 1 year onwards (respectively, P<0.01 and P<0.05). Renal plasma flow and anastomotic blood flow were not significantly higher in lacidipine-treated patients. Three patients on lacidipine therapy and four on placebo experienced treatment failure defined as an increase in serum creatinine from baseline of more than 60% (log-rank test: P=0.57). Study groups did not differ in acute rejection rate, trough blood cyclosporine concentrations, blood pressure, number of antihypertensive drugs, hospitalization rate, and adverse event rate. The use of calcium channel blockers in cyclosporine-treated renal recipients results in a significantly better allograft function at 2 years and this effect is independent of blood pressure lowering.