Effects Of Calcium Channel Antagonists Research Articles

Comparative assessment of effects of calcium channel antagonists, amlodipine, and cilnidipine, on QT interval in hypertensive patients - An observational study

Background: The duration of the QT interval as measured by 12-lead electrocardiography is a measure of myocardial repolarization and is widely used to describe cardiac abnormalities, to determine the presence of cardiac toxicity and to evaluate drug safety. In hypertension, the QT interval is a predictor of the risk of both coronary events and cardiovascular death, after adjusting for the effects of additional risk factors. According to AHA and JNC VIII calcium channel blockers are first-line drug in the treatment of hypertension. The equipotent antihypertensive effect of cilnidipine and amlodipine in their equivalent dose has been demonstrated in number of studies. Aims and Objectives: To compare and evaluate the effects of calcium channel antagonists amlodipine and cilnidipine on QT interval among hypertensive patients. Materials and Methods: A total of 258 patients were screened, examined, and enrolled as study participants during that period. The enrolled patients were then divided as (1) hypertensive patient (n = 159) - selected patients received either amlodipine (2.5–10 mg) or cilnidipine (5–20 mg) with or without angiotensin receptor blocker (ARB) and (2) hypertensive with controlled diabetic patients (n = 99) - selected patients received either amlodipine (2.5–10 mg) or cilnidipine (5–20 mg) with or without ARB along with antidiabetic medication. Calculated by Bazett’s formula (most commonly used) = QT Interval/√ (relative risk [RR] interval) where RR interval = 60/heart rate, normal QTc ≤440 ms. The QT interval was measured at the baseline and after 12 months of treatment for hypertensive patients. Results: There was extremely significant QTc reduction was seen with cilnidipine therapy and significant elevation seen by amlodipine treatment but without any clinical relevance. While comparing the effect of amlodipine and cilnidipine, extremely significant as well as clinically relevant difference between the two treatments was noted. Conclusions: From this study, it can be concluded that cilnidipine reduces QTc interval, and hence is a better choice over amlodipine for patients suffering from long QT interval.

On a sugary-relationship between caspases and lamins

On a sugary-relationship between caspases and lamins

STUDY ON EXPLORATION OF EFFECT OF VOLTAGE GATED CALCIUM CHANNEL BLOCKERS ON THE ANTI DEPRESSANT ACTION OF IMIPRAMINE AND ALPRAZOLAM

Background: Imipramine is a tricyclic anti depressant drug. Alprazolam is a benzodiazepine sedative drug, but it has also antidepressive action. Voltage gated calcium channel blockers are well known antihypertensive, anti anginal, anti arrhythmic drugs. Objective: In this study I explored the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine. Materials And Methods: Despair swim test model was used to study the anti depressive effect on the Male Sprague-Dawley rats. Rats were divided into nine groups (n = 6 per group). One group received a single dose of Tween 80 solution, as because it was used as vehicle for all the drugs; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine); two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil); four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups). Drug administration was performed concurrently on the nine groups. Results: The anti depressant action of both imipramine and alprazolam was confirmed by this study. . Both verapamil & nifedipine delays the onset of immobility, when administered separately. Verapamil potentiate the antidepressive effect of both imipramine & alprazolam. When nifedipine was combined with imipramine , there was delay in the onset of immobility and was greater than their single use. . Either imipramine or nifedipine produced a delay in the onset of immobility of 75% and 81%, respectively, compared to the control( p< 0.05) and combining nifedipine with imipramine led to a delay of 73% in the onset of immobility compared to the control ( p< 0.05).  Conclusion: Combination of voltage gated calcium channel blocker with imipramine and alprazolam was some positive effect on the antidepressant action. Key words: Anti depressive action, Sedative, Voltage gated calcium channel, Alprazolam, Imipramine.

The effects of calcium channel antagonists on coronary nitrite outflow in isolated rat heart.

The aim of the study was to compare the effects of Ca2+ channel antagonists on coronary endothelial L-arginine/NO system in isolated rat heart. The hearts of male Wistar albino rats (n = 36, age 8 weeks, body mass 180-200 g) were perfused according to Langendorff technique at gradually increased coronary perfusion pressure (CPP) which induced flow-dependent NO release (nitrite outflow). The experiments were performed during control condition or in the presence of different Ca2+ channel antagonists: nifedipine (CAS 21829-25-4, 30 nmol/l), diltiazem (CAS 42399-41-7, 3 mumol/l), verapamil (CAS 52-53-9, 0.4 mumol/l) or amlodipine (CAS 88150-42-9, 100 nmol/l) were administered separately. Also, nifedipine or amlodipine were administered in combination with an inhibitor of nitric oxide synthase (NOS), L-NAME (NG-nitro-L-arginine-methylester, 30 mumol/l). Coronary flow (CF) varied in autoregulatory range from 3.93 +/- 0.25 ml/min/g wt at 50 cmH2O to 4.49 +/- 0.31 ml/min/g wt at 90 cmH2O. In autoregulatory range nitrite outflow varied from 1.80 +/- 0.22 nmol/min/g wt at 50 cmH2O to 2.21 +/- 0.25 nmol/min/g wt at 90 cmH2O and was strictly parallel with the CPP-CF (coronary perfusion pressure/coronary flow) curve. The autoregulatory range of CF was significantly extended (40-100 cmH2O) under the influence of nifedipine. Hemodynamic effects were accompanied by significant changes in nitrite outflow in all groups except for the verapamil group. Nifedipine and diltiazem induced statistically significant increases of nitrite outflow in coronary venous effluent, strictly parallel with the CPP-CF curve, from 58% at 120 cmH2O to 190% at 40 cmH2O and from 74% at 120 cmH2O to 166% at 40 cmH2O, respectively. On the contrary, amlodipine induced significant reduction of nitrite outflow which was stronger at the lower value of CPP (44-46% at 40-80 cmH2O), compared to the higher value of CPP (32-37% at 100-120 cmH2O). When L-NAME was applied in combination with nifedipine or amlodipine, CF was significantly reduced with parallel changes in nitrite outflow. The results show that Ca2+ channel antagonists (verapamil, diltiazem, nifedipine and amlodipine) strongly influence the coronary endothelial L-arginine/NO system in isolated rat heart leading to the difference in nitrite outflow.

Effects of calcium channel antagonists on the motivational effects of nicotine and morphine in conditioned place aversion paradigm

The motivational component of drug withdrawal may contribute to drug seeking and relapse through the negative reinforcement-related process; thus, it is important to understand the mechanisms that mediate affective withdrawal behaviors. The present study was undertaken to examine the calcium-dependent mechanism of negative motivational symptoms of nicotine and morphine withdrawal using the conditioned place aversion (CPA) paradigm. Rats were chronically treated with nicotine (1.168 mg/kg, free base, s.c., 11 days, three times daily) or morphine (10 mg/kg, s.c., 11 days, twice daily). Then, during conditioning, rats pre-treated with nicotine or morphine received a nicotinic receptor antagonist mecamylamine (3.5 mg/kg) or an opioid receptor antagonist naloxone (1 mg/kg) to precipitate withdrawal in their initially preferred compartment, or saline in their non-preferred compartment. Our results demonstrated that after three conditioning sessions, mecamylamine induced a clear place aversion in rats that had previously received nicotine injections, and naloxone induced a significant place aversion in rats that had previously received morphine injections. Further, the major findings showed that calcium channel antagonists, i.e., nimodipine, verapamil and flunarizine (5 and 10 mg/kg, i.p.), injected before the administration of mecamylamine or naloxone, attenuated nicotine or morphine place aversion. As an outcome, these findings support the hypothesis that similar calcium-dependent mechanisms are involved in aversive motivational component associated with nicotine a morphine withdrawal. We can suggest that calcium channel blockers have potential for alleviating nicotine and morphine addiction by selectively decreasing the incentive motivational properties of both drugs, and may be beneficial as smoking cessation or opioid dependence pharmacotherapies.

Electrophysiological effects of calcium channel antagonists, isradipine and nicardipine on cardiac action potential repolarization

Electrophysiological effects of calcium channel antagonists, isradipine and nicardipine on cardiac action potential repolarization

Combined L-/T-Type Calcium Channel Blockers

Opening of the voltage-dependent Ca2+ channels permits influx of Ca2+ across the plasma membrane, triggering diverse physiological processes. These channels are widely distributed in the cardiovascular system, constituting the main route for Ca2+ entry essential for excitation and contraction. Ten unique α1 subunits, grouped in 3 families (CaV1, CaV2, and CaV3), that encode the low-voltage–activated T-type and the high-voltage–activated L-, N-, P/Q- and R-type Ca2+ channels, have been identified.1,2 L-type Ca2+ channels are predominantly expressed in the hearts and peripheral vasculature and serve as the preferred molecular target of the initial Ca2+ channel antagonists in the treatment of hypertension.3 Recently, a growing body of evidence has accumulated depicting important roles of T-type Ca2+ channels in the regulation of cardiovascular function, such as generation of pacemaker potential and regulation of arterial resistance.3,4 T-type Ca2+ channels are found in various cell types, including neurons, cardiomyocytes, vascular smooth muscle cells, and endocrine cells, where they participate in a variety of physiological processes, such as low-threshold Ca2+ spike generation, action potential firing, pacemaking, impulse conduction, maintenance of myogenic tone, cell proliferation, and hormone secretion.1 In addition to their predominant role in the regulation of vascular function, T-type Ca2+ channels are also involved in cardiomyocyte growth and survival.3 T-type Ca2+ channel blockers are capable of interrupting certain pathological hypertrophic signaling pathways, including calcineurin-mediated nuclear factor of activated T cells–3 activation.1 The importance of voltage-dependent Ca2+ channels is demonstrated by the clinical efficacy of Ca2+ channels blockers in certain disease conditions, as well as the widespread distribution and function of these channels.1 Three classes of chemically distinct L-type Ca2+ channel blockers have been widely used clinically depending on their biophysical and conformation-dependent interactions …

The change of F-actin and actin binding protein in intstinal epithelial cells under the ischemia and anoxia injury

Objective To investigate the relationship between the apoptosis and the change of F-actin and actin binding protein in intstinal epithelial cells (IEC) under the ischemia and anoxia injury, and the effect of calcium channel antagonist. Methods Primary culture of rat IECs and ischemia and an-oxia injury model in vitro were established. IECs were divided into 8 groups : group A ( control group), group B (ischemia group) ,group C (anoxia group) ,group D (ischemia and anoxia group) ,group A1 ( A +2 mg/L Verapamil) ,group B1 (B +2 mg/L Verapamil) ,group C1 (C +2 mg/L Verapamil) ,group D1 ( D + 2 mg/L Verapamil). Apoptosis rate (AR) was determined by flow cytometry. F-actin, talin and α-ac-tin were observed by LSCM. Results The AR in groups B, C and D was significantly higher than in group A (P < 0.05). The AR in groups B1, C1 and D1 was lower than in groups B. C and D ( P < 0.05 ). The form and arragement of F-actin, talin and α-actin in groups B, C and D were changed with the decrease of fluorescence intensity compared with group A (P < 0.01 ), the most significant in group D. The change in groups B1, C1 and D1 was reduced and the fluorescence intensity was increased as compared with the cor-responding injury groups (P < 0.05). Conclusion The ischemia and anoxia injury results in the break-down of F-actin and actin binding protein, which is related to the apotosis of IEC. Calcium channel antago-nist can decrease AR and reduce the change of these cytoskeleton. Key words: Intestinal epithelial ceils ; Ischemia; F-actin

Calcium-Channel Antagonists Inhibit Marble-Burying Behavior in Mice

In the present study, we examined the effects of calcium-channel antagonists on marble-burying behavior, which is an animal model of obsessive-compulsive disorder. Amlodipine (10 mg/kg, i.p.), cilnidipine (10 mg/kg, i.p.), nilvadipine (3 and10 mg/kg, i.p.), and flunarizine (30 mg/kg, i.p.) significantly inhibited marble-burying behavior in mice. These results suggest that calcium channels may be involved in the marble-burying behavior.

Effect of calcium-channel antagonist on repolarization heterogeneity of ventricular myocardium in an in vitro rabbit model of long QT syndrome

Intracellular Ca(2+) and Ca(2+)-dependent signaling molecule play an essential role in the genesis of long-QT (LQT) syndrome-related ventricular arrhythmias. The effect of calcium-channel antagonist verapamil on repolarization heterogeneity of ventricular myocardium was assessed in an in vitro rabbit model of LQT syndrome. By using the monophasic action potential (MAP) recording technique, MAPs of epicardium, mid-myocardium and endocardium were simultaneously recorded by specially designed plunge-needle electrodes across the left ventricular free wall in rabbit hearts perfused by Langendorff method with standard Tyrode's solution. Bradycardia was induced by complete ablation of atrioventricular node. A catheter was introduced into the right ventricle to pace at the cycle lengths (CLs) of 1500, 1000, and 500 ms, successively. Quinidine (2 micromol/L) prolonged QT interval and ventricular MAP duration (MAPD), and increased transmural dispersion of repolarization (TDR) in a reverse rate-dependent fashion in isolated rabbit heart. No polymorphic ventricular tachycardias were induced under this condition. The effective free therapeutic plasma concentrations of verapamil (0.01-0.05 micromol/L) used in this experiment had no effect on quinidine-induced changes of QT interval, MAPD and TDR. This study demonstrated that, in this model of LQT syndrome, blockade of calcium-channel with verapamil had no effect on quinidine-induced changes of repolatiation heterogeneity of ventricular myocardium.

Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group). One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine); two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil); four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups). Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility) when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect). This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

Effects of calcium channel blockers on antidepressant action of Alprazolam and Imipramine

Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group). One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine); two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil); four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups). Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility) when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect). This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

Rate Control

The control of ventricular rate plays an important role in the management of patients with atrial fibrillation, decreasing symptoms and improving cardiac function, exercise capacity, and quality of life.1–3 Oral or intravenous agents are routinely administered to achieve adequate control of the ventricular rate by modulating atrioventricular nodal function. The systemic effects of calcium channel antagonists and β-adrenergic receptor antagonists on blood pressure and other adverse effects, however, may limit use of these agents in some patients. In other patients, it may be difficult to achieve adequate rate control with the use of pharmacological agents. Article p 2383 In their article in this issue of Circulation , Sigg et al4 describe the novel approach of delivering pharmacological agents via a luminal catheter secured to the region of the atrioventricular node. Using a steerable electrophysiological catheter, they locate the His bundle potential and the coronary sinus ostium and display these positions in 2 orthogonal planes. The luminal catheter is screwed into the myocardium, and third-degree atrioventricular block resulting from the injection of a 1-mg dose of acetylcholine is used to confirm the proper positioning of the luminal catheter. The authors demonstrate that varying degrees of atrioventricular nodal blockade may be achieved by continuous infusion of acetylcholine at rates between 10 and 200 μg/min. In comparison, the intravenous injection of 1 mg acetylcholine did not cause atrioventricular block in any animal, demonstrating that a significant part of the effect of the direct luminal infusion was local. The authors provide histological evidence that the luminal catheter was positioned within or near the edge of the triangle of Koch, confirming the accuracy of the positioning method. In addition, no significant histological …

Reinstatement of nicotine-conditioned place preference by drug priming: Effects of calcium channel antagonists

Reinstatement of drug-seeking behaviour in animals is relevant to drug relapse in humans. In the present study, we used the conditioned place preference paradigm to investigate the establishment, extinction, reinstatement and cross-reinstatement of nicotine-induced place conditioning in rats. Nicotine produced a place preference to the initially less-preferred compartment paired with its injections during conditioning (0.5 mg/kg, i.p., three drug sessions). Once established, nicotine place preference was extinguished by repeated training. Following this extinction phase, the reinstatement of place conditioning was investigated. For this purpose, nicotine-experienced rats were challenged with nicotine (0.5 mg/kg, i.p.) or morphine (10 mg/kg, i.p.). These priming injections of both drugs renewed a marked preference for the compartment previously paired with nicotine. In the second step, we examined the influence of the calcium channel antagonists, nimodipine (10 and 20 mg/kg, i.p.) and flunarizine (5 and 10 mg/kg, i.p.), on the reinstatement of nicotine-conditioned place preference induced by priming doses of nicotine and morphine. It was shown that the calcium channel blockers dose dependently attenuated the reinstatement of nicotine place preference induced by both drugs. These findings support the hypothesis that similar neural calcium-dependent mechanisms are involved in nicotine- and morphine-induced reinstatement. Finally, the conditioned place preference paradigm appears to be a useful tool for studies of the relapse of drug-seeking behaviour in laboratory animals.

Effects of Cilnidipine on Fibrinolysis in Chinese Hypertensive Patients

Hypertension is an important risk factor for myocardial infarction and stroke. Accumulating data support the association of blood pressure and impairment of fibrinolysis in hypertensive patients. Fibrinolysis plays a pivotal role in atherogenesis, but there are few studies that focus on evaluating the effect of calcium channel antagonists on fibrinolysis in hypertensive patients, and the results are controversial. The aim of this study was therefore to investigate the effects of cilnidipine on fibrinolysis in Chinese hypertensive patients. This study was an open-label, paired trial that included 43 patients with mild-to-moderate hypertension. After a 2-week placebo washout period, patients were treated with cilnidipine 5mg daily for 8 weeks. Venous blood was taken before and after treatment between 8am and 9am, after an overnight fast. Plasma tissue plasminogen activator (tPA) antigen and plasminogen activator inhibitor type 1 (PAI-1) antigen were measured by ELISA and plasma angiotensin II was measured by radioimmunoassay. After treatment with cilnidipine for 8 weeks, plasma tPA antigen level increased significantly (from 12.12 +/- 6.77 ng/mL pre-treatment to 16.12 +/- 11.89 ng/mL post-treatment, p < 0.05), and the PAI-1 antigen level remained unaffected. There were no significant changes in plasma angiotensin II. Systolic and diastolic blood pressures were significantly decreased without changes in heart rate. These data suggest that in hypertensive patients, a population with impaired fibrinolysis, cilnidipine may improve the fibrinolytic balance, and that cilnidipine is effective in treating hypertension without causing reflex tachycardia.

Vascular Effects of Calcium Channel Antagonists: New Evidence

Calcium channel antagonists have a well-established role in the management of cardiovascular diseases. L-type calcium channels in vascular cells are a key therapeutic target in hypertension and are the preferred molecular target of the initial calcium channel antagonists. However, third-generation dihydropyridine (DHP) calcium channel antagonists, including manidipine, nilvadipine, benidipine and efonidipine, appear to have effects in addition to blockade of the L-type calcium channel. Voltage-gated calcium channels are widely expressed throughout the cardiovascular system. They constitute the main route for calcium entry, essential for the maintenance of contraction. Cardiac and vascular cells predominantly express L-type calcium channels. More recently, T-type channels have been discovered, and there is emerging evidence of their significance in the regulation of arterial resistance. A lack of functional expression of L-type channels in renal efferent arterioles may be consistent with an important role of T-type channels in the regulation of efferent arteriolar tone. Although the exact role of T-type calcium channels in vascular beds remains to be determined, they could be associated with gene-activated cell replication and growth during pathology. The three major classes of calcium channel antagonists are chemically distinct, and exhibit different functional effects depending on their biophysical, conformation-dependent interactions with the L-type calcium channel. The DHPs are more potent vasodilators, and generally have less cardiodepressant activity than representatives of other classes of calcium channel antagonist such as diltiazem (a phenylalkylamine) and verapamil (a benzothiazepine). In contrast to older calcium channel antagonists, the newer DHPs, manidipine, nilvadipine, benidipine and efonidipine, dilate not only afferent but also efferent renal arterioles, a potentially beneficial effect that may improve glomerular hypertension and provide renoprotection. The underlying mechanisms for the heterogenous effects of calcium channel antagonists in the renal microvasculature are unclear. A credible hypothesis suggests a contribution of T-type calcium channels to efferent arteriolar tone, and that manidipine, nilvadipine and efonidipine inhibit both L and T-type channels. However, other mechanisms, including an effect on neuronal P/Q-type calcium channels (recently detected in arterioles), the microheterogeneity of vascular beds, and other types of calcium influx may also play a role. This article presents recent data about the expression and physiological role of calcium channels in arteries and the molecular targets of the calcium channel antagonists, particularly those exhibiting distinct renovascular effects.

The radial artery as a coronary bypass conduit: dealing with hyperreactivity

The radial artery as a coronary bypass conduit: dealing with hyperreactivity

0337 The effect of calcium channel antagonist on the c-fos and c-jun mRNA expressions in rat dorsal root ganglia

0337 The effect of calcium channel antagonist on the c-fos and c-jun mRNA expressions in rat dorsal root ganglia

Muscarinic receptor subtype determines vulnerability to amyloid beta toxicity in transfected cos-7 cells.

Research has suggested that there are age-related increases in neuronal sensitivity to insult from oxidative stress (OS) and that the CNS alterations seen in Alzheimer disease (AD) and vascular dementia (VaD) are superimposed upon declining nervous and vascular systems. Since muscarinic receptors (mAChR) may be important in regional sensitivity, regulation of micro- circulation, and in various aspects of both neuronal (AbetaPP processing) and vascular functioning, we postulated that the various mAChR subtypes may show differential sensitivity to OS. Indeed, recent findings indicated that M1, M2, or M4 AChR-transfected COS-7 cells showed greater OS sensitivity [as reflected in Ca2+ buffering (i.e., the ability to extrude or sequester Ca2+ following oxotremorine-induced depolarization)] than those transfected with M3 or M5 AChR when exposed to dopamine. Interestingly, the results from the present study indicate that similar findings were also observed when the cells were exposed to Abeta 25-35 and Abeta 1-40 showed similar effects on M1 and M3 AChR. No effects were seen with Abeta 35-25 or Abeta 40-1. Thus, cells transfected with M1, M2 or M4 AChR showed greater disruptions in calcium regulation (as assessed via fluorescent imaging analysis prior to and following 750 microm oxotremorine) than those transfected with M3 or M5 AChR. We also examined the effects of calcium channel antagonists (e.g., Nifedipine) or antioxidants (vitamin E) in protecting against the deleterious effects of Abeta. Results are discussed in terms of differences in MAChR structure that could lead to selective Abeta effects and the possible implications on memory and AbetaPP processing.

Effects of Calcium Channel Antagonists on Left Ventricular Hypertrophy and Diastolic Function in Patients with Essential Hypertension

Hypertensive patients characteristically exhibit left ventricular (LV) hypertrophy and diastolic dysfunction. The effects of antihypertensive agents on LV hypertrophy and diastolic dysfunction do not always correlate with the degree of blood pressure reduction, but their effects on the sympathetic nervous system and renin–angiotensin system (RA system) are thought to be important. We investigated the effects of amlodipine and cilnidipine, N‐ and L‐type calcium channel antagonists that suppress both blood pressure elevation and sympathetic activities, on LV hypertrophy and diastolic function. Patients with essential hypertension were randomly assigned to receive either amlodipine, cilnidipine or nifedipine CR (which does not block N‐type calcium channels) for 6 months. The LV mass index was determined using M‐mode echocardiography. The E/A ratio, i.e., the ratio of maximum amplitude between the early diastolic wave (E wave) and the atrial systolic wave (A wave) in the LV inflow pattern, and the deceleration time for the E wave were determined using pulse Doppler echocardiography. Systolic and diastolic blood pressures significantly decreased from the baseline values in all three groups, with no significant differences among the groups. The LV mass index had significantly decreased when it was evaluated 3 months after the initiation of treatment in the cilnidipine group and when it was evaluated 6 months after the initiation of treatment in the amlodipine group; only a slight decrease was observed in the nifedipine CR group. A significant decrease in the deceleration time and a significant increase in the E/A ratio were observed after 3 months of treatment in the cilnidipine and amlodipine groups but not in the nifedipine CR group. Thus, the effects of long‐acting calcium channel antagonists on hypertensive LV hypertrophy and LV diastolic function varied from one antagonist to the other. Left ventricular hypertrophy and diastolic function improved in the cilnidipine and amlodipine groups, but not in the nifedipine CR group. These results indicate that the suppression of sympathetic nerve activity by the blockade of N‐type calcium channels contributes to the improvement of LV hypertrophy and diastolic function.