Role Of Calcium Channel Blockers Research Articles

Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging

Objective: To investigate the association between use of calcium channel blockers (CCB), dihydropyridine (DHP) or nondihydropyridine (nonDHP) type CCB and risk of developing Alzheimer’s Disease (AD) or mortality. There is evidence suggesting that calcium plays a key role in changes in the brain leading to AD. Previous reports suggest a possible role for CCB in the treatment of AD. However, there are some indications that CCB increase mortality in patients with cardiac disease. Methods: Subjects were 1092 participants in the Baltimore Longitudinal Study of Aging (BLSA) older than 60 years of age. Data on CCB use was collected prospectively for up to 19 years. Cox proportional hazards regression was used to estimate relative risks (RR) and confidence intervals (CI) of AD and mortality associated with use of CCB or use of only DHP or nonDHP-CCB. Analyses were adjusted for gender, education, smoking, blood pressure and history of heart problems. Results: Use of DHP-CCB was not associated with a significantly reduced risk of AD compared to non-users, although the estimate of the RR was low with DHP-CCB (RR = 0.30, 95% CI = 0.07–1.25, P = 0.10). Use of nonDHP-CCB was not associated with reduced risk of AD and the estimate of the RR risk was close to one (RR = 0.82, 95% CI = 0.37–1.83, P = 0.63). In addition, there was no increase in mortality among users of DHP-CCB (RR = 0.64, 95% CI = 0.32–1.29, P = 0.21) or nonDHP-CCB (RR = 1.10, 95% CI = 0.65–1.87, P = 0.72). Conclusion: Users of DHP-CCB and nonDHP-CCB in this study did not have a significantly reduced risk of AD.

Has the role of calcium channel blockers in treating hypertension finally been defined?

Several large, prospective, randomized, clinical outcome trials have shown that calcium channel blockers are effective and safe antihypertensive drugs compared with placebo and reduce the cardiovascular morbidity and mortality of treated patients. In other studies, when 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. However, considering all the evidence available today, 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. In addition, when a calcium channel blocker is indicated for better blood pressure control, its use should not be withheld for safety concerns.

Role of calcium channel blockers in the future, in view of the INSIGHT Study

The data from The International Nifedipine Intervention as a Goal in Hypertension Treatment (INSIGHT) Study indicate that effectively reducing blood pressure can decrease the incidence of cardiovascular events in high risk patients with concomitant pathology, including diabetes and hypercholesterolemia, as well as in smokers and those with poor family history. Old and new antihypertensive drugs were similar in preventing cardiovascular mortality as major events. The glomerular filtration rate of patients on co-amilozide went down compared to those on nifedipine. Metabolic parameters, as expected, were not disturbed during treatment with calcium channel blockers, in contrast to the high-dose diuretic-treated population. Ankle edema induced by nifedipine was very disturbing. It can be concluded that overall calcium channel blockers are neither better nor worse than conventional therapy, allowing for possible small differences in stroke (advantage to calcium channel blockers) and myocardial infarction (advantage to diuretics). Thus, calcium channel blockers should be included in the future among the first choice drugs.

Effects of antihypertensive drugs in experimental type 2 diabetes-related nephropathy

It has been extensively reported that antihypertensive drugs reduce proteinuria and glomerulosclerosis (GS) in many experimental nephropathies and in humans. However, the role of calcium channel blockers (CCBs) in the prevention of proteinuria and GS remains controversial and in most cases only dihidropyridine-CCBs are studied. Few studies have reported whether the time at which drug administration is initiated plays a role in the reduction of proteinuria and GS. Fifty-six male Obese Zucker rats (OZR) were used as a model of spontaneous type 2 diabetes-related nephropathy. Biochemical and histological analysis were performed to compare the efficacy of a non-dihydropyridine-CCB diltiazem [DZM; 100 mg/kg body weight (BW)/day], an ACEI quinapril (10 mg/kg BW/day), or both in diminishing proteinuria and GS, and to determine their role in effective prevention and treatment. Only quinapril was able to diminish proteinuria. As far as histological lesions, both treatments were effective, although only quinapril prevented GS. The combination of quinapril plus DZM did not demonstrate any beneficial effects. Surprisingly, quinapril ameliorated the damage of podocytes whereas DZM did not, thus leading to doubt concerning the efficiency of DZM in long-term studies. Nonetheless, the combination of quinapril plus DZM demonstrated a greater reduction in podocyte damage than treatment with DZM alone, which shows an interesting association in the prevention of longer-term glomerular damage. Few differences were found between prevention and treatment. Quinapril, but not DZM, was able to diminish proteinuria in OZR. Both treatments were effective in diminishing GS, although only quinapril totally prevented it. The combination of both drugs prevented long-term glomerular damage, which is intriguing.

Optimizing cardiovascular outcomes in progressive renal insufficiency: the importance of blood pressure, antihypertensive therapy and the role of calcium channel blockers

NephrologyVolume 7, Issue s2 p. S52-S53 Optimizing cardiovascular outcomes in progressive renal insufficiency: the importance of blood pressure, antihypertensive therapy and the role of calcium channel blockers Lloyd Ibels, Lloyd Ibels Department of Renal Medicine, The University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, AustraliaSearch for more papers by this author Lloyd Ibels, Lloyd Ibels Department of Renal Medicine, The University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, AustraliaSearch for more papers by this author First published: 09 October 2008 https://doi.org/10.1046/j.1440-1797.7.s.21.x Dr Lloyd Ibels, Head, Department of Renal Medicine, Clinical Professor of Medicine, The University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume7, Issues2May 2002Pages S52-S53 RelatedInformation

Optimizing cardiovascular outcomes in progressive renal insufficiency: the importance of blood pressure, antihypertensive therapy and the role of calcium channel blockers

Optimizing cardiovascular outcomes in progressive renal insufficiency: the importance of blood pressure, antihypertensive therapy and the role of calcium channel blockers

Calcium channel blockers intake and psoriasis: a case-control study.

In vitro evidence suggests that intracellular calcium metabolism influences keratinocyte differentiation. However, only a few reports have described exacerbation of psoriasis or psoriasiform eruptions due to intake of calcium channel blockers. We conducted a case-control study to evaluate the association between exposure to calcium channel blockers and psoriasis. Data were obtained through a retrospective assessment of the files of 150 patients hospitalized for psoriasis or psoriasiform eruptions and 150 matched control patients. Exposure to calcium channel blockers was recorded in case and control patients. It was found that 13/150 patients hospitalized for psoriasis consumed calcium channel blockers. Calcium channel blockers were associated with precipitation of new-onset psoriasis (n = 2), as well as with the exacerbation of psoriasis (n = 11). The calcium channel blockers were as follows: nifedipine (n = 10), felodipine (n = 2) and amlodipine (n = 1). The median latent period between the beginning of intake of calcium channel blockers and precipitation or exacerbation of psoriasis was 28 months (range 4-143 months). A stepwise multivariate logistic regression analysis demonstrated that intake of calcium channel blockers was significantly associated with psoriasis, as compared to the control group (p = 0.018). Our study implies a possible role of calcium channel blockers as precipitating or exacerbating factors in patients with psoriasis.

Mechanisms of plaque stabilization for a charged calcium channel blocker in coronary artery disease.

Coronary artery disease (CAD) results from atherosclerosis, a systemic vascular disorder that is the leading cause of death and disability throughout much of the developed world. Because cellular changes associated with vulnerable atherosclerotic plaque are characterized by a loss of normal calcium regulation, there is strong interest in a potential antiatherosclerotic role for calcium channel blockers. This hypothesis has been supported by investigational studies conducted in well-defined cellular and animal models of atherosclerosis. In addition, several clinical studies have tested the benefit of calcium channel blockers among patients with mild-to-moderate CAD. More recent trials have shown reductions in cardiovascular events after treatment with amlodipine, a long-acting, dihydropyridine-type calcium channel blocker. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) demonstrated that patients with documented CAD treated with amlodipine experienced marked reductions in cardiovascular events compared with patients receiving placebo. Amlodipine also was associated with significant slowing of carotid atherosclerosis, an important surrogate marker for CAD, independent of blood pressure modification. These results have renewed interest in potential plaque stabilization properties of third-generation calcium channel blockers and their possible therapeutic role in CAD.

Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye.

Vasospasm can have many different causes and can occur in a variety of diseases, including infectious, autoimmune, and ophthalmic diseases, as well as in otherwise healthy subjects. We distinguish between the primary vasospastic syndrome and secondary vasospasm. The term "vasospastic syndrome" summarizes the symptoms of patients having such a diathesis as responding with spasm to stimuli like cold or emotional stress. Secondary vasospasm can occur in a number of autoimmune diseases, such as multiple sclerosis, lupus erythematosus, antiphospholipid syndrome, rheumatoid polyarthritis, giant cell arteritis, Behcet's disease, Buerger's disease and preeclampsia, and also in infectious diseases such as AIDS. Other potential causes for vasospasm are hemorrhages, homocysteinemia, head injury, acute intermittent porphyria, sickle cell disease, anorexia nervosa, Susac syndrome, mitochondriopathies, tumors, colitis ulcerosa, Crohn's disease, arteriosclerosis and drugs. Patients with primary vasospastic syndrome tend to suffer from cold hands, low blood pressure, and even migraine and silent myocardial ischemia. Valuable diagnostic tools for vasospastic diathesis are nailfold capillary microscopy and angiography, but probably the best indicator is an increased plasma level of endothelin-1. The eye is frequently involved in the vasospastic syndrome, and ocular manifestations of vasospasm include alteration of conjunctival vessels, corneal edema, retinal arterial and venous occlusions, choroidal ischemia, amaurosis fugax, AION, and glaucoma. Since the clinical impact of vascular dysregulation has only really been appreciated in the last few years, there has been little research in the according therapeutic field. The role of calcium channel blockers, magnesium, endothelin and glutamate antagonists, and gene therapy are discussed.

Is there a role for calcium channel blockers in congestive heart failure?

Over the past several decades, we have made great strides in understanding the pathophysiology of heart failure and have developed new therapeutic targets based on utilizing several different models in clinical trials. Currently, standard therapy involves angiotensin-converting enzyme inhibitors and beta-blockers. In an effort to further reduce mortality, investigators focused on other vasodilators (calcium channel blockers) that might prove to be advantageous when added to standard therapy. Large- scale trials showed that the calcium channel blockers did not have a specific role in mortality reduction, but the third-generation dihydropyridine calcium channel blockers were safe to use in patients with heart failure.

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg x kg(-1) plus 0.04 mg x kg(-1)x min(-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 microg x kg(-1) plus 2 microg x kg(-1) x min(-1)), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 +/- 0.4 to 13.8 +/- 0.8 mA, p < 0.001) and lengthens VCT (28 +/- 3 to 44 +/- 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 +/- 0.6 and 8.4 +/- 0.7 mA, n.s.) or VCT (between 30 +/- 2 and 34 +/- 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.

Benefit of antihypertensive treatment in the diabetic patients enrolled in the Systolic Hypertension in Europe (Syst-Eur) trial.

In this review we attempt to determine the role of calcium channel blockers in preventing cardiovascular sequelae in patients with both hypertension and diabetes mellitus. The data have been collected from three sources: post-hoc analyses of subgroups of diabetic patients in placebo-controlled hypertension trials (SHEP, Syst-Eur, Syst-China); stepped-care blood pressure-oriented trials (HOT); and comparative trials focusing primarily on metabolic aspects and intermediate endpoints (ABCD, FACET). On balance, the data seem to indicate that long-acting calcium channel blockers score remarkably well in preventing cardiovascular complications in diabetic hypertensive patients.

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg x kg(-1) plus 0.04 mg x kg(-1)x min(-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 microg x kg(-1) plus 2 microg x kg(-1) x min(-1)), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 +/- 0.4 to 13.8 +/- 0.8 mA, p < 0.001) and lengthens VCT (28 +/- 3 to 44 +/- 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 +/- 0.6 and 8.4 +/- 0.7 mA, n.s.) or VCT (between 30 +/- 2 and 34 +/- 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.

The Role of Calcium Channel Blockers in Restoration and Maintenance of Sinus Rhythm in Patients with Atrial Fibrillation

The Role of Calcium Channel Blockers in Restoration and Maintenance of Sinus Rhythm in Patients with Atrial Fibrillation

Effects of antihypertensive therapy on progression of diabetic nephropathy

There is a clear relationship between hypertension and the microvascular complications of diabetes. Genetic predisposition to hypertension has been correlated to the risk of diabetic nephropathy in type I diabetes, and hypertension is a well known risk factor for developing nephropathy in patients with type II diabetes. Multiple studies have emphasized the importance of hypertension on renal disease progression, and blood pressure control with conventional antihypertensive drugs slows the rate of renal function loss in diabetic nephropathy. Furthermore, evidence of the role of renin-angiotensin system (RAS) on progression of renal damage has focused much interest on the therapeutic action of the RAS blockade. In patients with type I diabetes, blocking the RAS with angiotensin converting enzyme (ACE) inhibitors prevents progression from microalbuminuria to overt nephropathy, and in overt nephropathy decreases the gradual loss of renal function beyond its blood pressure lowering effect. Less clinical information is available in type II diabetic nephropathy, but our experience and some recent studies suggest that ACE inhibitors also have a renoprotective action in type II diabetes. The role of calcium channel blockers in diabetic nephropathy is not clear. Several short-term studies with the first generation dihydropyridine calcium antagonists showed a lower effect on urinary albumin excretion and a more rapid progression to renal failure than with ACE inhibitors. However, other calcium channel blockers, particularly of the non-dihydropyridine type, have been shown to have a beneficial effect on diabetic nephropathy, decreasing proteinuria and slowing progression.

Calcium channel blockers in cardiac failure

Congestive cardiac failure is an increasingly prevalent syndrome associated with a high morbidity and mortality. The role of calcium channel blockers in the treatment of heart failure is unclear. The potential benefits of these agents derive not only from their vasodilator properties, but also from anti-ischemic effects, beneficial effects on endothelial function and the development of atherosclerosis, and favorable effects on calcium cycling at a molecular level. Pitted against this array of potential benefits are direct negative inotropic effects and the potential for neuroendocrine activation. Treatment with short-acting dihydropyridine agents has not resulted in long-term clinical benefits in patients with cardiac failure. Diltiazem may be beneficial in patients with nonischemic heart failure, and verapamil has a neutral effect in cardiac failure, although it may have a role in combination with ace inhibition. To date, amlodipine has been associated with the most promising results, with evidence of a mortality benefit in nonischemic heart failure. Mibefradil is of no benefit in the management of heart failure, although the trend toward increased mortality in the treatment arm of the Mortality Assessment in Congestive Heart Failure (MACH)-1 trial may have been due to drug interactions. The potential role of calcium blockers in diastolic dysfunction and in combination with ace-inhibition requires further study.

Interaction between Calcium Channel Blockers and Sweetening Agents on Morphine-Induced Analgesia in Mice by Formalin Test

1. Calcium is known to be an important ion in the modulation of nociception and inflammation. Previous research has shown that mice drinking sweet-tasting solutions such as sucrose, saccharin and aspartame exhibit significant changes in morphine-induced analgesia in both phases of the formalin test. 2. In this study, the role of calcium channel blockers on the effectivity of a 12-day regimen of different sweetening agents (sucrose 32%, saccharin 0.08% and aspartame 0.16%) on the alteration of the morphine response has been investigated. 3. Male albino mice weighing 20–27 g were used for experiments. Animals were given 12 days to adapt to dietary conditions. Animals were given morphine (1.5, 3, 6, 9 mg/kg) subcutaneously 30 min before observation. Nifedipine (5 mg/kg), verapamil (5 mg/kg) and diltiazem (10 mg/kg) were administered intraperitoneally 20 min before morphine injection. 4. Recording of the early phase started immediately and lasted for 10 min after formalin injection. Recording of the late response started 20 min after formalin injection and lasted for 10 min. 5. Calcium channel blockers potentiated the antinociceptive effects of sweetening agents and diminished the antagonistic effects of these compounds on morphine-induced analgesia in the early and late phases of the formalin test. 6. It is proposed that calcium has a role for the interactive effects of sweetening agents and morphine on pain sensitivity.

New Views on the Role of Calcium Channel Blockers in the Treatment of Atrial Fibrillation

New Views on the Role of Calcium Channel Blockers in the Treatment of Atrial Fibrillation

Cholesterol, calcium and atherosclerosis: is there a role for calcium channel blockers in atheroprotection?

It is well known that the atherogenic dyslipidemias of either elevated serum LDL or reduced HDL levels correlate with the degree and severity of atherosclerosis. However, how this leads to atherogenesis is poorly understood. A role for cellular oxidative stress mediated by oxidized LDL has gained widespread acceptance, but this pathway is unlikely to be the sole atherogenic signal. Recent evidence obtained from arterial smooth muscle cells (SMC) and endothelial cells (EC) is consistent with another pathway that may explain, in part, the early alterations contributing to the initiation of cellular atherogenic modifications. This pathway involves enrichment of the cell plasma membrane with cholesterol. In SMC, in vitro (cell culture) and in vivo (cholesterol feeding) experiments demonstrate that cholesterol enrichment of the SMC membrane occurs rapidly and is associated with an increase in membrane bilayer width, calcium permeability, and cell proliferation. Removal of excess membrane cholesterol with human HDL restores these alterations, suggesting that this membrane structural `defect' mediates these changes in cell function. In vitro, the increased calcium permeability is inhibitable by calcium channel blockers (CCBs), but in vivo, a calcium `leak' pathway develops that is virtually uninhibitable. It is not surprising that the literature on the application of CCBs for atheroprotection is not wholly convincing. However, with the advent of the new third generation of CCBs, new hope arises. One of the first CCBs of this generation is amlodipine (Norvasc), a charged dihydropyridine that has a remarkable pharmacologic profile. First, it is markedly lipophilic allowing it to partition readily into cell membranes. Second, in the membrane it has the ability to re-order, or restore, the `swollen' membrane bilayer back to normal in atherosclerotic SMC. Third, it has potent antioxidant properties. Fourth, it appears to inhibit the expression of a variety of genes implicated in atherogenesis. Fifth, it is a CCB. Amlodipine has demonstrated atheroprotection in both rabbit and subhuman primate models of this disease. We propose that cellular alterations induced by enrichment of the cell membrane with cholesterol, which appears to modulate SMC to the atherosclerotic phenotype, are inhibitable by amlodipine through a combination of its varied pharmacologic properties. The potential for atheroprotection with amlodipine is currently being investigated in a human trial (PREVENT trial) and the results of this trial will determine the relevance of the preclinical findings to humans.

Accelerated arteriosclerosis after transplantation: the possible role of calcium channel blockers

The major factor limiting the long-term success of cardiac transplantation is the development of accelerated arteriosclerosis that occurs in the coronary arteries of the cardiac allograft. Transplant arteriosclerosis is characterized by diffuse, uniform, concentric narrowing of the artery by a proliferative, fibrocellular intima. The etiology of transplant arteriosclerosis is thought to be immune-mediated, and endothelial cells, smooth muscle cells, and inflammatory cells participate in the progression. Based on data derived from studies of conventional atherosclerosis, in which calcium channel blockers (CCBs) have demonstrated beneficial effects, preliminary studies designed to determine if CCBs might affect transplant arteriosclerosis similarly have been performed in animal models as well as in a limited number of cardiac transplant patients. Amlodipine suppressed transplant arteriosclerosis in one animal study, while diltiazem preserved vasodilatory responses in another animal study. Small prospective trials and retrospective studies in humans have shown that CCBs have a favorable effect on the development of transplant arteriosclerosis. While no work has been directed specifically at determining the mechanisms by which CCBs might prevent transplant arteriosclerosis, there are several likely candidates. These include preservation of endothelial function, suppression of smooth muscle cell migration and proliferation, production of extracellular matrix, and regulation of lipid metabolism and certain components of the immune system.