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PubMed2003

N-terminal pro-brain natriuretic peptide as a diagnostic marker of early pulmonary artery hypertension in patients with systemic sclerosis and effects of calcium-channel blockers.

OBJECTIVE: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of early pulmonary artery hypertension (PAH) and to study changes in the levels of this marker following treatment with dihydropyridine-type calcium-channel blocker (DTCCB) in patients with systemic sclerosis (SSc). METHODS: We evaluated 40 consecutive SSc patients who had been hospitalized for followup care (mean +/- SD age 56 +/- 11 years and mean +/- SD duration of cutaneous disease 9 +/- 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but who had no clinical symptoms of heart failure and had a normal left ventricular ejection fraction. At baseline, 10 patients had PAH, defined as a systolic pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography. Levels of NT-proBNP were determined at baseline (after discontinuation of DTCCB treatment for 72 hours), after taking 3 doses of DTCCB following treatment reinitiation (assessment 1), and after 6-9 months of continuous DTCCB treatment (assessment 2) in the 20 patients who attended regular appointments (including the 10 patients with PAH at baseline). RESULTS: At baseline, 13 patients had high NT-proBNP values for their ages. High NT-proBNP levels identified patients with PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive value of 69.2%, and a negative predictive value of 96%. The NT-proBNP level correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of patients with PAH and high levels of NT-proBNP had decreased from 9 of 10 to 2 of 10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10 patients; P = 0.06). CONCLUSION: NT-proBNP is a useful biologic marker that can be used to diagnose early PAH in SSc patients without clinical heart failure. Measurement of NT-proBNP may be valuable for the evaluation of treatment with DTCCB and vasodilators in patients with PAH.

Aged↗
PubMed1991

[Effect of angiotensin converting enzyme inhibitor and calcium channel blocker on renal function of spontaneously hypertensive rat].

Effect of angiotensin converting enzyme inhibitor (ACEI) and calcium channel blockers (CaB) on renal blood flow (RBF), glomerular filtration rate (GFR), and autoregulation (AR) of RBF were studied on the uninephrectomized spontaneously hypertensive rat (SHR) under the conditions of high (H) and low (L) salt loading. SHR was given with 0.9% or 0.09% NaCl solution as drinking water (GH, GL). Each group was divided into three groups for treatment with enalapril (Enp) and nitredipine (Nit); i.e. Enp group (GHE, GLE), Nit group (GHN, GLN) and control group (GHC, GLC). After 6 weeks, inulin clearance (Cin) was determined and RBF was measured by means of an electromagnetic flow meter. The renal arterial pressure was lowered by clamping and changes in RBF and AR were examined. Cin showed higher values of 1.85 and 1.69 ml/min in GHN and GLN, as compared to be 1.33 and 1.28 ml/min in GHC and GLC (p less than 0.01). Filtration fraction (FF) showed lower values of 0.18 and 0.20 ml/min in GHE and GLE (p less than 0.01), whereas 0.29 and 0.30 in GHC and GLC respectively. RBF was markedly lower at 7.4 ml/min in GLC as compared to 9.9 ml/min in GHC (p less than 0.01). In GH, GHE showed a higher value of 11.6 ml/min, as compared to GHC (p less than 0.01). In GL, comparing with GLC the value was much higher of 12.1 ml/min in GLE (p less than 0.01). AR of RBF diminished in GLC at higher blood pressure as compared to GHC (p less than 0.01). It was maintained at lower blood pressure in GLE (p less than 0.01), but there were no significant differences between four groups; i.e. GLN, GHC, GHE and GHN. In summary, low salt loading reduced RBF and suppressed AR. Enp elevated RBF, lowered FF and caused AR to be maintained even at lower blood pressure. Nit elevated RBF and GFR without changing FF, and did not suppress AR. These results indicate that, in hypertension complicated with moderate dysfunction, both ACEI and CAB are expected to exhibit the beneficial effects on maintenance of renal circulation, despite though the different mechanism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Effect of calcium channel blockers on vertebral bone marrow perfusion of the lumbar spine.

PURPOSE: To investigate the effect of calcium channel blockers on blood perfusion of vertebral bone marrow in the lumbar spine. MATERIALS AND METHODS: Sixteen healthy volunteers (eight men and eight women) underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging of the lumbar spine. One hundred twenty minutes after the first MR examination, each subject ingested 10 mg sublingual nifedipine before undergoing a second MR examination 20-25 minutes later. Semiquantitative (peak enhancement ratio and enhancement slope) and quantitative (amplitude and rate constant of the exchange [K(out)]) parameters were analyzed with the time-intensity curve. Data obtained before and after administration of nifedipine were compared. The Wilcoxon signed rank test and Spearman rank correlation test were used. RESULTS: Median peak enhancement ratio of vertebral bodies decreased from 0.60 (mean +/- SD, 0.68 +/- 0.29) to 0.51 (mean, 0.56 +/- 0.24) after administration of nifedipine. Median and mean decreases were 0.11 and 0.12 +/- 0.15, respectively, and the percentage difference was 17% (P =.005). A P value of less than.05 was considered to indicate a statistically significant difference. Median enhancement slope changed from 0.45 (mean, 0.45 +/- 0.13) to 0.41 (mean, 0.40 +/- 0.24). Median and mean changes were 0.05 and 0.04 +/- 0.23, respectively, and the percentage difference was 9% (P =.334). Median amplitude changed from 0.059 (mean, 0.059 +/- 0.028) to 0.045 (mean, 0.048 +/- 0.023). Median and mean changes were 0.008 and 0.011 +/- 0.025, respectively, and the percentage difference was 18% (P =.072). Median K(out) changed from 0.068 (mean, 0.063 +/- 0.018) to 0.067 (mean, 0.066 +/- 0.028). Median and mean changes were 0.011 and 0.004 +/- 0.028, respectively (P =.404). Nifedipine affected peak enhancement ratio significantly but did not affect enhancement slope, amplitude, or K(out). Data before and after administration of nifedipine showed no differences between men and women. Spearman rank correlation coefficients suggest no significance between the differences in heart rate and blood pressure and the differences in peak enhancement ratio, enhancement slope, amplitude, or K(out). CONCLUSION: After sublingual administration of nifedipine, the peak enhancement ratio of vertebral bone marrow decreased.

Adult↗
PubMed1983

Calcium channel blockers for the treatment of coronary artery spasm: rationale, effects, and nursing responsibilities.

Coronary artery spasm is recognized as a cause of ischemic heart disease, producing a syndrome of the variant form of angina that occurs at rest. Spasm also may play a role in other types of rest angina (unstable angina) and exertional angina. Calcium is essential for the basic tonus of vascular smooth muscle. The accentuated contraction that occurs in coronary artery spasm is the result of an increase in intracellular calcium ions. Current therapy is aimed at blocking the slow calcium currents that are responsible for electrical activation and contraction of smooth muscle cells. A marked coronary vasodilatation is produced with calcium channel blockers, thus demonstrating effective therapy for coronary artery spasm. A similar effect is achieved by nitrates, and these agents will continue to have a role in the therapy of spasm. Calcium channel blockers produce beneficial effects on myocardial oxygen supply and demand and, therefore, are also useful in the prevention of classic exertional angina caused by fixed obstruction. Verapamil and diltiazem possess electrophysiologic effects and have, in addition, proved useful in the treatment of supraventricular dysrhythmias.

Calcium↗
PubMed2005

Effect of irbesartan monotherapy compared with ACE inhibitors and calcium-channel blockers on patient compliance in essential hypertension patients: a multicenter, open-labeled, three-armed study.

OBJECTIVES: This multicenter, three-armed, open-labeled study investigated patient compliance of patients receiving irbesartan, angiotensin-converting enzyme (ACE) inhibitors or calcium-channel blockers (CCB) for essential hypertension for a 6-month period. Patients were either newly diagnosed or switched from existing antihypertensive medication due to lack of efficacy or side-effects. METHODS: Patients were started monotherapy with irbesartan (n=377), ACE inhibitors (n=298) or CCB (n=308) and were reevaluated on 1st, 3rd, and 6th months of the treatment. The primary endpoint was patient compliance, assessed by proportion of patients who had taken their study medication every day. Efficacy was recorded as mean reductions in blood pressure and the proportion of patients whose blood pressure normalized. Tolerability was assessed by reported adverse events. RESULTS: Significantly more patients receiving irbesartan had complied with study medication after 3 and 6 months of treatment than ACE inhibitors or CCB. Significantly fewer patients receiving irbesartan needed to change their antihypertensive medication. All three study treatments exhibited similar efficacy profiles, but irbesartan had significantly less adverse events. CONCLUSIONS: This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments. Irbesartan is therefore a suitable first-line therapy for essential hypertension in everyday clinical practice.

Adult↗
PubMed1999

Different effects of L-type and T-type calcium channel blockers on the hypnotic potency of triazolam and zolpidem in rats.

We examined the effects of an L-type Ca2+ channel blocker, nilvadipine (0.5 and 2.0 mg/kg), and that of a T-type Ca2+ channel blocker, flunarizine (10.0 and 40.0 mg/kg), on the hypnotic potency of both a benzodiazepine (BZ)-hypnotic, triazolam (1.0 mg/kg), and a non-BZ hypnotic, zolpidem (20.0 mg/kg), in rats. The polysomnogram was recorded for 6 h after administration of the vehicle solution alone, or after one of the Ca2+ channel blockers, with or without one of the hypnotics. Both Ca2+ channel blockers prolonged the increased total time of non-rapid eye movement (non-REM) sleep induced by either hypnotic. In the case of triazolam, however, the non-REM sleep-enhancing effect induced by nilvadipine was greater than that induced by flunarizine. These findings indicate that the hypnotic action of triazolam is potentiated more strongly by an L-type Ca2+ channel blocker than by a T-type Ca2+ channel blocker.

Animals↗
PubMed2001

The calcium channel blocker controversy in patients with diabetic nephropathy: Is there an issue?

Chronic renal failure, proteinuria, and arterial hypertension run in parallel in the presence of diabetic nephropathy. New goal blood pressure levels have been established in diabetic patients: 130/85 mm Hg and 125/75 mm Hg depending on the level of proteinuria being below or above 1 g/d. New and lower threshold blood pressure (>130/85 mm Hg) to initiate pharmacologic therapy is required in the presence of diabetes mellitus in order to facilitate the strict blood pressure control that is required. It must be considered that both renal and cardiovascular protection are obtained with strict blood pressure control, which otherwise seems to require blockade of angiotensin II effects when proteinuria above 1 g/d is present. While awaiting the publication of long-term follow-up studies looking at renal and cardiovascular outcome in diabetic and other nephropathies in which calcium channel blockers are compared with other antihypertensive drugs, calcium channel blockers will remain the drugs needed to attain the expected goal blood pressure in diabetics, both alone (in the absence of microalbuminuria or macroalbuminuria) or in combination, particularly with angiotensin converting enzyme inhibitors.

Blood Pressure↗
PubMed1994

Effect of pinaverium and other calcium channel blockers on contraction of isolated gastric antral smooth muscle cells caused by gastrointestinal hormones.

Gastrointestinal hormones, gastrin, cholecystokinin (CCK), and motilin, are known to induce contraction of digestive smooth muscle cells from various species. In this paper, we studied the effect of calcium channel blockers, diltiazem, nicardipine, and pinaverium on the hormone-dependent contraction of smooth muscle cells isolated from rabbit antrum. Gastrin, CCK-8, and motilin caused dose-dependent contraction with EC-50 values in the physiological range (10-100 pM). This contractile effect was dependent upon extracellular calcium for gastrin and CCK-8 but not for motilin. When used alone, calcium channel blockers diltiazem, nicardipine, but not pinaverium, caused a weak but significant contraction of the cells. Pinaverium inhibited both gastrin- and CCK-8-induced contractions with IC-50 values of 1 nM and it was much less potent in the inhibition of motilin-induced contractions (IC-50 = 25 nM). The effect of pinaverium was equivalent to that of diltiazem in the inhibition of CCK-8- or gastrin-induced contractions. Both drugs were slightly more potent than nicardipine (IC-50 = 10 nM versus 1 nM for pineaverium and 5 nM for diltiazem). In contrast, diltiazem and pinaverium were less potent against motilin stimulation, diltiazem being 5 times more potent than pinaverium. In conclusion, it appears that since Ca2+ antagonists pinaverium, diltiazem and nicardipine inhibited contraction of smooth muscle cells stimulated by gastrointestinal hormones, "L-type" calcium channels of the plasma membrane might also be regulated through occupation of gastrin or CCK receptors.

Animals↗
PubMed2001

End organ protection by calcium-channel blockers.

In recent years, much attention has been given to end organ protection by antihypertensive, anti-heart failure, and anti-ischemic medications. This review describes the available information on end organ protection by calcium-channel blockers (CCBs). In normotensive patients and patients with hypertension treated with long-acting dihydropyridines, medial thickness was thinner than in patients treated with atenolol or in untreated hypertensive patients. Long-term treatment was associated with significant reduction in left ventricular mass. Calcium-channel blockers also improved endothelial-dependent relaxation and reversed the vasoconstrictive response to nitric oxide inhibitors. In diabetic patients, CCBs were effective in preserving kidney function and microalbuminurea. The combination of angiotensin-converting enzyme (ACE) inhibitors and CCBs was more effective than ACE inhibitors alone in preserving kidney function. In animal experiments, CCBs prevented development of coronary atheroschlerosis; however, in humans only limited data are available on their antiatherogenic effect. Some studies suggest that CCBs exert antiplatelets properties and may therefore be beneficial in patients with coronary artery disease.

Angina Pectoris↗
PubMed1984

Reduction of ischemic depolarization by the calcium channel blocker diltiazem. Correlation with improvement of ventricular conduction and early arrhythmias in the dog.

Calcium channel blockers suppress early ischemic arrhythmias, possibly by diminishing intracellular calcium overload and its effect on the ventricular action potential. To explore this, we compared the effects of diltiazem on ischemic "injury" potentials and ventricular fibrillation during serial coronary artery occlusions in dogs. Injury potentials and ventricular fibrillation were elicited every 15-25 minutes by simultaneous occlusion of the left anterior descending and circumflex arteries during rapid atrial pacing. DC epicardial electrograms were recorded differentially between the ischemic region and a small nonischemic region supplied by a proximal branch of the left anterior descending artery. Injury potentials developed with a uniform time course during five control occlusions, but were reduced by diltiazem infusion (0.5 mg/kg over 25 minutes) in each of eight dogs. The mean diastolic injury potential (T-Q depression) at 150 seconds of ischemia was 9.1 +/- 2.7 mV before diltiazem and 6.1 +/- 1.6 mV afterward (P less than 0.001). Diltiazem increased the mean time between coronary occlusion and ventricular fibrillation from 186 to 366 seconds (P less than 10(-5), but did not change the magnitude of the diastolic injury potential at onset of ventricular fibrillation. Diltiazem also delayed ischemia-induced conduction impairment to the same extent that it delayed injury potential development. In five dogs, the effect of diltiazem on regional blood flow near the epicardial electrodes was measured by infusion of radionuclide-labeled microspheres. Coronary occlusion reduced flow to the ischemic zone from 0.86 to 0.05 ml/min per g (P = 0.001). Diltiazem increased preocclusion flow by 11% (P = 0.03), but did not significantly alter flow during occlusion. Hemodynamic measurements show that diltiazem did not diminish cardiac work. Diltiazem therefore produced a flow-independent reduction of cellular depolarization during ischemia, which may be due to relief of calcium overload, and which may explain the antifibrillatory effect.

Action Potentials↗
PubMed2000

Therapeutic approaches to achieve desired blood pressure goals: focus on calcium channel blockers.

The new guidelines for blood pressure control recommended by the World Health Organisation, the International Society of Hypertension, and the JNC VI require that blood pressure be lowered to levels of < 130/85 mmHg in persons with either diabetes or renal insufficiency. A review of over 20 clinical trials performed over the last two decades indicates that an average of 62% of the participants required more than two medications to achieve a goal of < 140/90 mmHg. Thus, with the new guidelines it is clear that an even higher proportion of people will require at least two different medications to achieve this lower goal. Certain classes of antihypertensive medications are relatively more efficacious for lowering blood pressure in certain ethnic and racial groups, thus reducing the probability that two or more agents will be needed to achieve a stated blood pressure goal. This is exemplified by the effects of calcium channel blockers in African-Americans. However, even in these groups many require at least two different antihypertensive agents to achieve the blood pressure goal. The fixed-dose combinations of a calcium channel blocker and ACE inhibitor offer the advantages of complementary physiologic action, improved tolerability, lower side-effect profile, enhanced salutary effects on target organs, better compliance, and lower cost. Varieties of fixed-dose combination regimens for blood pressure lowering are available for clinical use. This article focuses on the subclasses of calcium channel blockers and their role in altering the natural history of both cardiovascular and renal disease. The article further discusses the role of fixed-dose agents with regard to their place in the antihypertensive armamentarium.

Antihypertensive Agents↗
PubMed1998

Calcium channel blockers and the risk of cancer: a preclinical assessment.

The preclinical evidence for a potential influence of calcium channel blockers (CCBs) on carcinogenesis is discussed in the light of a broad database from rodent carcinogenicity studies as well as literature data. In all bioassays performed in rats and mice on the dihydropyridine CCBs--nifedipine, nimodipine, nisoldipine, and nitrendipine--no evidence was found for a carcinogenic potential of these compounds. Calcium is an essential intracellular signal for cell proliferation and apoptosis. The crucial role of increased cell proliferation in all stages of carcinogenesis is well documented. Some indirect experimental evidence also points to a role of defective apoptosis in tumor promotion. CCBs uniformly inhibit cell proliferation, whereas the influence of CCBs on apoptosis is inconsistent, resulting in an inhibition or increase in apoptosis dependent on cell type. Accordingly, antitumorigenic effects of CCBs have been reported based on their antiproliferative action. A tumor-promoting effect of CCBs based on inhibition of apoptosis, however, remains purely speculative and, in fact, can be denied based on the results of in vivo bioassays. It is therefore concluded that there is no preclinical evidence that should give rise to concern over the carcinogenic potential of dihydropyridine-type CCBs.

Animals↗
PubMed1990

Inhibitory effects of endothelial cells and calcium channel blockers on platelet aggregation.

This study examined the effects of human umbilical vein endothelial cells (ECs) and calcium channel blockers (Ca2+ blockers), diltiazem, verapamil, and nicardipine, on platelet aggregation in vitro. ECs markedly inhibited the platelet aggregation induced by ADP, collagen, thromboxane A2 (TXA2), or thrombin. When platelets were incubated with ECs, the antiaggregatory activity reached a plateau within 5 to 10 min. As the number of ECs added to the platelet-rich plasma was increased, platelet aggregation declined progressively. The antiaggregatory activity of ECs was attenuated considerably by the addition of aspirin. All three Ca2+ blockers inhibited platelet aggregation in a dose-dependent manner. The combination of ECs and a Ca2+ blocker resulted in more potent inhibition of platelet aggregation than either alone, but the effects were not synergistic. Both ECs and Ca2+ blockers inhibited the synthesis of TXA2 during platelet aggregation. However, Ca2+ blockers did not significantly influence the production of prostaglandin I2 (PGI2) by ECs during incubation and aggregation. These results suggest that PGI2 is an important factor in endothelial antiaggregatory activity. Ca2+ blockers directly inhibit platelet aggregation by suppressing TXA2 formation, but do not appear to enhance the antiaggregatory activity of ECs.

6-Ketoprostaglandin F1 alpha↗
PubMed2004

Calcium channel blockers, either amlodipine or mibefradil, ameliorate renal injury in experimental diabetes.

BACKGROUND: Diabetic nephropathy is associated with increased albuminuria and accumulation of extracellular matrix proteins within the kidney. Clinical studies have shown some beneficial effects of calcium channel blockers (CCB) on diabetic nephropathy, even though they are generally considered to be less renoprotective than agents that interrupt the renin angiotensin system. However, effects of CCBs on renal injury, and in particular, expression of extracellular matrix proteins in a model of normotensive diabetic nephropathy, are poorly characterized. METHODS: Experimental diabetes was induced by injection of streptozocin in Sprague-Dawley rats. Amlodipine, a CCB which blocks the L channel, and mibefradil, a CCB blocking the T as well as the L channels, were given to diabetic rats for six months. Albumin excretion rate (AER), pathologic injury, and expression of the extracellular matrix proteins, collagen I, and fibronectin were assessed. RESULTS: Increased AER in diabetic rats (13.2 x//1.3 mg/d, geometric mean x// tolerance factor) was attenuated by either amlodipine (3.2 x// 1.4 mg/d) or mibefradil (2.6 x// 1.4 mg/d). Increased glomerulosclerosis and tubulointerstitial injury in diabetic animals were attenuated by amlodipine and mibefradil. There was increased collagen accumulation in the kidney of diabetic rats as assessed by picro-sirius red staining. Gene expression of both collagen I and fibronectin were also increased in the kidneys from diabetic animals, as assessed by reverse transcription-polymerase chain reaction (RT-PCR). These markers of fibrosis were attenuated by treatment with either amlodipine or mibefradil. Blood pressure in diabetic rats (136 +/- 2 mm Hg) was modestly reduced by amlodipine (126 +/- 3 mm Hg) but not by mibefradil treatment (134 +/- 3 mm Hg). CONCLUSION: Calcium channel blockers attenuated albuminuria, pathologic injury, and accumulation of extracellular matrix proteins in this normotensive model of diabetic nephropathy. These findings suggest that CCBs may be useful in preventing pathologic injury in the diabetic kidney.

Albuminuria↗
PubMed1990

Age-related changes in the uptake of calcium channel blockers by brain capillary endothelial cells and synaptosomal fractions.

The effects of aging on the uptake of calcium channel blockers through brain capillaries to brain parenchyma were investigated. Two different piperazine derivatives, flunarizine and 1-[bis(fluorophenyl)-methyl]-4-(2,3,4-trimethoxybenzyl)piperazine (abbreviated as KB-2796), were orally administered to young and aged rats. The concentrations of the blockers in plasma, endothelial cells of the brain capillaries and synaptosomal fractions of the three brain regions were determined by high-performance liquid chromatography. Flunarizine was more incorporated into brain tissues than KB-2796 in both young and aged rats. The uptake efficiency of KB-2796 from the circulation to the brain decreased more remarkably than that of flunarizine in aged rats. The partition coefficients between n-octanol and water indicated that KB-2796 was less hydrophobic than flunarizine. These results suggest that the uptake of the chemicals seems to be influenced by their hydrophobicity and the age of animals given.

Aging↗
PubMed2000

Calcium channel blockers and pain therapy.

This review focuses on the advances in the development of N-type calcium channel blockers as analgesic agents over the last 2 years. Firstly, it highlights the clinical progress with SNX-111 (Ziconotide; Elan Pharmaceuticals, Smithfield, RI) and then secondly, it outlines the various approaches being taken by researchers to design orally active, selective, small molecule modulators without the perceived disadvantages associated with SNX-111.

Animals↗
PubMed1996

Calcium channel blockers induce thymic apoptosis in vivo in rats.

We investigated the in vivo effect of structurally different calcium channel blockers (CCB) on rat thymus. Administration of verapamil (40 mg/kg ip), diltiazem (90 mg/kg ip), nifedipine (15 mg/kg ip), or nicardipine (10 mg/kg ip) induced apoptotic indices of 4.3, 4.0, 2.0, and 6.5, respectively, compared to 0.5 in the saline-treated control rats. Apoptosis was assessed by morphology and the apoptotic index was calculated using a computer-assisted image analyzer. Diltiazem had a rapid and substantial effect as evidenced by apoptosis at 1.5 hr and a 36% decrease in thymus weight by 24 hr. We were uncertain about the mechanisms by which CCB induced thymic apoptosis in vivo since in vitro studies have shown that increases in intracellular calcium cause apoptosis and that CCB prevent apoptosis. We sought insight into the mechanism by evaluating potential and known in vivo effects of these drugs. Neither verapamil nor diltiazem was found to elevate serum cortisol levels, a known trigger for apoptosis. Hypotension, a known response to CCB, does not appear to be causal factor since the potent hypotensive agent sodium nitroprusside (10 microg/kg, iv) did not cause a significant increase in thymic apoptosis. Calcium signaling may be important since the calmodulin antagonist chlorpromazine (60 mg/kg ip) was found to induce a 15-fold increase in apoptosis. Our observations suggest that calcium signaling is necessary for the survival of the T lymphocytes in the thymus.

Animals↗