Abstract:
:To evaluate the role of intracellular calcium and particularly Ca2+-uptake in the initiation of lymphocyte mitogenesis, the effect of mibefradil, which blocks both L- and T-type calcium channels with a more selective blockade of T-type channels, on the proliferation of human peripheral blood mononuclear cells (PBMCs) is compared with the effect of nifedipine, which blocks only the L-type calcium channel. The rate of [3H]thymidine incorporation into control and concanavalin A-stimulated PBMCs in the presence or absence of the calcium channel blockers mibefradil or nifedipine (1, 10, or 50 microM), and of the intracellular calcium antagonist 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8; 1, 10, 25, or 50 microM) was assayed in the cells cultured for 3 days. The cellular cytotoxicity and the cell number in growing cultures also was determined in mibefradil- or nifedipine-treated control or stimulated cells. Restoration of the proliferative response in mibefradil- or nifedipine-treated cells was investigated by addition of exogenous interleukin-2. Interleukin-2-receptor expression in the cells was monitored by using anti-activated T-cell antigen (Tac) antibody, and the interleukin-2 production in the cell supernatants of the cultures was determined by an enzyme-amplified sensitive immunoassay. Mibefradil and nifedipine concentration-dependently reduced the cell number and the [3H]thymidine incorporation or the de novo DNA synthesis in control and concanavalin A-stimulated human PBMCs. Mibefradil exhibited a more pronounced inhibition of the proliferation of human PBMCs than did nifedipine. The inhibitory effect of mibefradil or nifedipine on DNA synthesis was dependent on the timing of treatment with the drugs. The inhibitory effect of mibefradil or nifedipine on the lymphoproliferative response was nearly abolished if the drugs were added 20 h after cell stimulation. A markedly reduced inhibitory effect was found when mibefradil or nifedipine was added 1-7 h after cell stimulation. However, regardless of time of addition, TMB-8 caused a persistent inhibition of the proliferation of human PBMCs. The inhibitory effect of mibefradil or nifedipine on the proliferation of human PBMCs is nearly abolished by addition of the calcium channel activator Bay K 8644. The proliferative response of mibefradil- or nifedipine-treated cells is restored by addition of exogenous interleukin-2. The normal expression of interleukin-2 receptors was preserved, whereas the interleukin-2 production was blocked in the presence of mibefradil or nifedipine. Our data show that mibefradil has a more pronounced inhibitory effect on the proliferation of human PBMCs than nifedipine and that this inhibitory effect on DNA synthesis is dependent on the timing of treatment with both drugs.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Lijnen P,Fagard R,Petrov Vdoi
10.1097/00005344-199904000-00012subject
Has Abstractpub_date
1999-04-01 00:00:00pages
595-604issue
4eissn
0160-2446issn
1533-4023journal_volume
33pub_type
杂志文章abstract::Insulin resistance is associated with endothelial dysfunction and increased production of the pro-inflammatory vasoconstrictor peptide endothelin-1 (ET-1). The aim of this study was to test the hypothesis that blockade of ET receptors results in enhanced endothelium-dependent vasodilatation (EDV) in individuals with i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000210070.47205.16
更新日期:2006-03-01 00:00:00
abstract::Drug-induced delayed cardiac repolarization is a recognized risk factor for proarrhythmia and is associated with block of IKr (the potassium current encoded by the human ether-a- go-go-related gene [hERG]). To evaluate the utility of 2 in vitro assays widely used to assess delayed repolarization, we compared the effec...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200403000-00007
更新日期:2004-03-01 00:00:00
abstract::Cromakalim relaxes vascular smooth muscle by increasing potassium channel conductance, thus hyperpolarizing cell membranes. Its interactions in humans with the cardiovascular effects of norepinephrine, angiotensin II, and isoproterenol were investigated. Eight young normotensive male volunteers received on three diffe...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199112000-00003
更新日期:1991-12-01 00:00:00
abstract::The study was designed to assess the antihypertensive effect of combined angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) antagonism in patients with essential hypertension. Twenty patients with uncontrolled ambulatory diastolic blood pressure (BP) after 6 weeks of ACE inhibitor ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200006000-00017
更新日期:2000-06-01 00:00:00
abstract::Erythropoietin (EPO) has been linked to cardioprotective effects. However, its effects during the aging process are little known. We investigated the effect of EPO administration on hemodynamic parameters, cardiac function, oxidative damage, and erythropoietin receptor (EPOR) expression pattern in the hypovolemic stat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000666
更新日期:2019-05-01 00:00:00
abstract::Measurements of cerebrospinal fluid (CSF) catecholamines (CA) were made in an attempt to estimate the activity of central CA neurons in essential hypertension (EHT). CSF norepinephrine (NE), epinephrine (EPI), and dopamine (DA) levels were measured in 12 normotensive (age 36 +/- 3 years; SBP = 116 +/- 4 and DBP = 79 +...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract::Disruption of atherosclerotic plaques with associated thrombus is responsible for the majority of the acute coronary syndromes. Plaque instability is related closely to the degree of inflammation. Inflammatory cells within the plaque produce cytokines that inhibit collagen production by vascular smooth muscle cells an...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1998-01-01 00:00:00
abstract::Diabetic nephropathy is a major cause of end-stage renal failure and the mortality rate due to this disease is continuously progressing worldwide. The multifaceted signalling mechanisms have been identified to be involved in the pathogenesis of diabetic nephropathy. Despite the modern therapies like antidiabetics, ant...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181ad2190
更新日期:2009-08-01 00:00:00
abstract::Dietary omega-3 polyunsaturated fatty acids (PUFAs) are readily incorporated into heart and skeletal muscle membranes where, in the heart, animal studies show they reduce O2 consumption. To test the hypothesis that omega-3 PUFAs alter O2 efficiency in humans, the effects of fish oil (FO) supplementation on O2 consumpt...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3181911913
更新日期:2008-12-01 00:00:00
abstract::Milrinone, a newly developed analogue of amrinone, possesses potent positive inotropic effects. Electrophysiologic actions of the drug have thus far been reported in only one study conducted on canine Purkinje fibers. The present study used microelectrode techniques to evaluate the electrophysiologic effects of milrin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198503000-00021
更新日期:1985-03-01 00:00:00
abstract::The effects of nitrendipine, a new antihypertensive agent, have been examined using the isolated rabbit aortic strip stimulated with either noradrenaline (1.7 X 10(-8) - 1.7 X 10(-5) mol/L) or potassium (22.7-52.7 mmol/L). Nifedipine, verapamil, phentolamine, papaverine, and minoxidil were used as reference compounds....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::Inhibition of plasma angiotensin II generation does not fully explain the chronic hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. Therefore, the pattern of tissue ACE inhibition in rats was studied after oral administration of perindopril, a new ACE inhibitor. Tissue ACE was measured by quantita...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198812000-00013
更新日期:1988-12-01 00:00:00
abstract::This presentation has reviewed evidence from our laboratory that both structural and functional changes participate in the initiation and maintenance of hypertension in spontaneously hypertensive rats (SHR). Structural changes are present in the muscular arteries of the mesenteric and renal vasculature at 3- to 5-week...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198406004-00014
更新日期:1984-01-01 00:00:00
abstract::The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group....
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199007000-00012
更新日期:1990-07-01 00:00:00
abstract::Endothelin-1 (ET-1) stimulated cAMP formation in Chinese hamster ovary cells stably expressing human wild-type ET(A) (CHO/hET(A) cells) and inhibited the formation in cells expressing human wild-type ETB (CHO/hETB cells), suggesting a selective coupling of hET(A) and hETB with G alpha s and G alpha i, respectively. To...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHRs) chronically treated with the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (SHR-l). NG-nitro-L-arginine methyl ester (80 mg/L) administration for 3 ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31821324b6
更新日期:2011-05-01 00:00:00
abstract::As cyclic 3',5'-guanosine monophosphate (cGMP) is still discussed as a possible mediator of the negative inotropic effects of cholinergic agents, the influence of acetylcholine (ACh) on force of contraction and cGMP tissue levels was studied in isolated, electrically driven guinea pig auricles in the presence of methy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198611000-00009
更新日期:1986-11-01 00:00:00
abstract::Myocardial alpha 1-adrenoceptor number has been reported to increase during ischaemia in myocytes consequent to an increase in acyl carnitine levels. We investigated whether this phenomenon occurs in vivo and whether the novel antiischaemic agent ranolazine will protect against it. Thirty-minute occlusion of the left ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199306000-00004
更新日期:1993-06-01 00:00:00
abstract::Since the end of 1976 ten orally active converting enzyme inhibitors [SQ 14,225 (captopril), MK 421 (enalapril), MK 422, MK 521 (lysinopril), RHC 3659, CGS 13945, CGS 13928C, CGS 14824A, Hoe 498, S 9490-3, and Ro 31-2848] have been evaluated by our group in normal volunteers. Their ability to blunt the pressor respons...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198507001-00002
更新日期:1985-01-01 00:00:00
abstract::Relationships between lipoprotein fractions, lipoprotein lipase activities, thyroid hormones, and coronary lesion growth were studied among 35 male patients with severe coronary atherosclerosis, who had participated in the Leiden Intervention Trial, a lipid-lowering dietary intervention program. Coronary arteriography...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Radioligand binding studies have detected alpha1A- and alpha1B-adrenergic receptors (AR) in rat heart, but the ligands available for these studies lack the sensitivity and specificity needed to map possible differences in alpha1-AR subtype expression. We therefore used competitive reverse transcriptase-polymerase chai...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199807000-00018
更新日期:1998-07-01 00:00:00
abstract::The pharmacologic properties of a novel nonpeptide endothelin (ET) receptor antagonist, S-1255 ([R]-[+]-2-[benzo(1,3)dioxol-5-yl]-6-isopropyl-4-[4-methoxyphenyl]-2H-chromene-3-carboxylic acid), was studied. [3H]S-1255 specifically bound to porcine aortic smooth muscle membranes expressing only ET(A) receptors with a K...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200104000-00014
更新日期:2001-04-01 00:00:00
abstract::In conscious rats, intrathecal (i.t.) administration of norepinephrine (NE) produced pressor responses, whereas i.t. epinephrine (Epi) caused depressor responses at low doses (0.1-1 microgram) and pressor responses at a higher dose (10 micrograms). Epi administered i.t. produced bradycardia; however, NE caused tachyca...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199209000-00005
更新日期:1992-09-01 00:00:00
abstract::A number of studies using endothelin (ET) precursors, commonly termed big ETs, have revealed the presence of endothelin-converting enzyme (ECE) activity in various vascular and nonvascular preparations. Since then, more than one ECE has been cloned. It has also been observed that big ET-1 and big ET-3 are not converte...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00019
更新日期:1998-01-01 00:00:00
abstract::Isolated systolic hypertension (ISH) is a definite risk factor for cardiovascular complications (i.e., cardiac failure, coronary artery disease, and stroke) independent of diastolic elevation. The prevalence of ISH is estimated to be approximately 15-20% in the population above the age of 60 years, and increases with ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1994-01-01 00:00:00
abstract::Amylin is a 37-amino acid peptide that shares considerable homology with calcitonin gene-related peptide (CGRP). Both peptides exert glycoregulatory actions and produce vasodilation of the cardiovascular system. We wished to determine if amylin exerts vasodilatory action in the perfused mesenteric arterial bed in a ma...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199512000-00012
更新日期:1995-12-01 00:00:00
abstract:INTRODUCTION:We investigated the efficacy of carvedilol for preventing the recurrence of atrial fibrillation and reducing QT prolongation induced by bepridil. METHODS:We assigned 144 subjects with persistent atrial fibrillation. The subjects were divided into 3 groups: carvedilol plus bepridil, candesartan plus beprid...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/FJC.0b013e3182790692
更新日期:2013-01-01 00:00:00
abstract::Although evidence has been accumulated to support a role of endothelin-1 (ET-1) in cardiac hypertrophy, details of the pathophysiological significance of ET-1 in cardiac hypertrophy remain to be elucidated. In the present study, we investigated the effects of the vasodilator hydralazine on the blood pressure, cardiac ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00054
更新日期:2000-11-01 00:00:00
abstract::Abdominal aortic aneurysms (AAA) is a multifactorial vascular disease with a high rate of mortality and brings heavy burden to both human and society. The pathological process behind AAA is complex. Elastin degradation, chronic inflammation, and vascular smooth muscle cell phenotypic modulation are involved in AAA for...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000785
更新日期:2020-03-01 00:00:00
abstract::KATP channels are a complex of regulatory sulfonylurea receptor subunits and the pore-forming inward rectifiers such as Kir6.1. Using the whole-cell patch-clamp technique, we investigated the interaction of nicotine with the Kir6.1 subunit as well as the underlying mechanism. Stable expression of Kir6.1 in HEK-293 cel...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000159046.35241.4e
更新日期:2005-05-01 00:00:00