Abstract：
:The cardiovascular properties of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a novel nonglycoside , noncatechol cardiotonic agent, were investigated in vitro and in vivo by both intravenous and oral administration. Ro 13-6438 increased tension development of isolated guinea pig left atria in a concentration-dependent manner with an EC50 of 30 microM, but had no stimulant effect on the spontaneous rate of right atria. The positive inotropic effect of Ro 13-6438 was additive to that of ouabain (0.1 microM); Ro 13-6438 suppressed the arrhythmogenic activity of high concentrations of ouabain (10 microM). IN anesthetized open-chest dogs 10-300 micrograms/kg Ro 13-6438 i.v. produced a significant and dose-dependent increase in myocardial force, with a duration of action exceeding 60 min following the highest dose. It also slightly increased heart rate, cardiac output, and blood flow. Ro 13-6438 decreased systolic and diastolic blood pressure, left ventricular end-diastolic pressure, and total peripheral resistance. Thus, the direct positive inotropic effects of Ro 13-6438 were supported by a decrease in preload and afterload. In chronically instrumented, conscious dogs Ro 13-6438 increased myocardial contractility after administration of 0.03-0.3 mg/kg i.v. or 3-10 mg/kg p.o. The effects persisted for greater than 8 h after oral administration of 10 mg/kg. The inotropic effects were accompanied by a modest increase in heart rate, which, however, had a clearly shorter duration of action than the former.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Eigenmann R,Gerold M,Holck Mdoi
10.1097/00005344-198405000-00021subject
Has Abstractpub_date
1984-05-01 00:00:00pages
511-9issue
3eissn
0160-2446issn
1533-4023journal_volume
6pub_type
杂志文章abstract：:Histamine receptors are present in adrenergic terminals, and histamine is reported to inhibit release of the neurotransmitter norepinephrine (NE) at certain neuroeffector junctions. However, a physiological role for histamine in modifying adrenergic neurotransmission has not been established. To examine the interactio...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198705000-00012
更新日期：1987-05-01 00:00:00
abstract：:We studied the inotropic and possible antioxidant effects of levosimendan in human atrial strips, before and after induction of oxidative stress induced by H2O2. Levosimendan (10(-9) to 10(-6) M) increased contractions induced by electrical stimulation (ES) in human atrial strips. The maximal positive inotropic effect...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e318123fbf9
更新日期：2007-10-01 00:00:00
abstract：:Acute myocardial infarction (AMI) is known to alter the pharmacokinetics of several antiarrhythmic agents. To study the effects of AMI on the kinetics of mexiletine (MEX), a single intravenous dose of 200 mg MEX HCl was infused over 30 min in 11 patients with AMI. The study was performed within 24 h of the onset of pa...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
abstract：:Plasma-membrane receptors for angiotensin II (AII) have been identified in many AII-responsive tissues involved in the control of blood pressure via direct or indirect actions on vascular contractility. The specific, high-affinity receptors for AII in adrenal zona glomerulosa, vascular smooth muscle, kidney, brain, an...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-198406004-00004
更新日期：1984-01-01 00:00:00
abstract：:Acute angiotensin-converting enzyme inhibitors (ACEIs) have been found to induce natriuresis in humans as well as in experimental animals. However, the tubular sites involved have not been precisely evaluated in humans. Using both free-water and lithium clearance, the latter as a marker of proximal tubular reabsorptio...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:The effects of the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril, HOE 498, and its prodrug on reperfusion arrhythmias after 15 min of coronary ligation were investigated in the isolated rat heart. Drug concentrations were equipotent in their effect on angiotensin I pressor response. Furthermore, ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
abstract：:Calcium-antagonist drugs are therapeutic agents of first choice in patients with coronary artery disease. We have reviewed a number of clinical trials in which the safety and efficacy of calcium blockers have been tested and discuss the established clinical effects of these compounds, which range from relief of angina...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1992-01-01 00:00:00
abstract：:We studied the effect of an intravenous (i.v.) infusion of diltiazem (15 micrograms/kg/min) given for 1 week on several cardiovascular parameters, renal blood flow, and electrolyte and urinary excretion in chronically instrumented DOCA-salt hypertensive dogs. On the first recording session, 24 h after diltiazem infusi...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198806000-00015
更新日期：1988-06-01 00:00:00
abstract：:The aim of the present work was to examine the effects of 4'-N-benzoyl staurosporine (CGP 41251), a protein kinase C inhibitor with broad antiproliferative activity in many cell lines, on the rat isolated heart contractility under normoxic and hypoxic conditions. Additionally, we examined the effects of CGP 41251, WB-...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200106000-00011
更新日期：2001-06-01 00:00:00
abstract：:The effect of the new vasodilatory and antianginal compound, bepridil (CERM-1978), was examined on the electrical activity of the vascular smooth muscle of isolated dog coronary arteries. Tetraethylammonium (10 mM) was used to induce excitability in the muscle in the form of Ca2+-dependent overshooting action potentia...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198107000-00024
更新日期：1981-07-01 00:00:00
abstract：:Baboons were given eight doses of clonidine hydrochloride (0.04--40 micrograms/kg) via indwelling femoral venous catheters. Systolic and diastolic blood pressures and heart rates were assessed for time course, magnitude of change, time-to-peak change, and duration of effect at each dosage level. The response to clonid...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198209000-00024
更新日期：1982-09-01 00:00:00
abstract：:We investigated the characteristics of 125I-AII binding to rat adrenal and bovine cerebellar membranes in the presence and absence of new nonpeptide angiotensin II (AII) receptor ligands. The imidazole AII ligands, DUP753 and WL19, both produced biphasic competition curves to 125I-AII binding in rat adrenal glomerulos...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199102000-00001
更新日期：1991-02-01 00:00:00
abstract：:Several reports suggest that when diuretics are added to nifedipine (N), they do not exert any additional hypotensive effect to that produced by N alone. We present the first double-blind, crossover trial to investigate this interaction. Twenty-four black patients with moderate to severe essential hypertension entered...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1987-01-01 00:00:00
abstract：:CGS 26303 has previously been shown to inhibit human endothelin converting enzyme-1 (ECE-1) with an IC50 of 410 nM and to be efficacious in several animal disease models. However, it is a more potent inhibitor of neutral endopeptidase 24.11 (NEP) with an IC50 of 1 nM. The aim of this study was to optimize CGS 26303 fo...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200036051-00014
更新日期：2000-11-01 00:00:00
abstract：:Endothelial dysfunction is the pathophysiologic principle involved in the initiation and progression of arteriosclerosis, thus endothelial function serves as a "barometer" for cardiovascular health that can be used for the evaluation of new therapeutic strategies. This review provides an introduction to the concept of...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-200606001-00007
更新日期：2006-01-01 00:00:00
abstract：:Simvastatin (SV), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity inhibits migration and proliferation of vascular smooth muscle cells (SMC). To investigate whether these effects of SV are related to inhibition of cell calcium mobilization, cultured SMC obtained from rat aorta were l...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199603000-00011
更新日期：1996-03-01 00:00:00
abstract：:High blood pressure (BP) is associated with increased risk of vascular disease, including myocardial infarction and stroke. Since drugs that lower BP will reduce the risk of those complications of hypertension that are due to high pressure (strokes due to small-vessel disease, including lacunar infarction and intracer...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1987-01-01 00:00:00
abstract：:The electrophysiologic effects of acutely and chronically administered amiodarone on canine Purkinje fibers were assessed using microelectrode techniques to record intracellular action potentials. Chronically treated dogs received amiodarone for 3 weeks (serum levels, 0.91 +/- 0.09 microgram/ml or 1.42 X 10(-6) M). Ac...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:Endothelin-1[1-31] is a recently discovered member of the endothelin family with vasoactive properties in several animal models and in man in vivo. It is generated from big endothelin-1 by human mast cell chymase and may be a novel intermediary peptide in the production of endothelin-1[1-21]. Given that both big endot...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/01.fjc.0000166233.11336.67
更新日期：2004-11-01 00:00:00
abstract：:The structure-activity relationships of phosphoramidon analogues for inhibition of endothelin-converting enzyme (ECE), neutral endopeptidase 24.11 (NEP), and angiotensin-converting enzyme (ACE) were compared. Phosphoramidon inhibited ECE, NEP, and ACE activities with IC50 values of 3.5, 0.034, and 78 microM, respectiv...
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 tested the hypothesis that the 5-HT transporter (5-HTT) is present and functional in peripheral arterial smooth muscle. In aorta and mesenteric resistance arteries, real time RT-PCR and western analyses indicated the presence of 5-HTT mRNA and a 74 kDa 5-HTT protein. Immunohistochemistry localized the transporter t...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200406000-00006
更新日期：2004-06-01 00:00:00
abstract：:Data from 49 men and 48 women included in the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study in Perth, Western Australia, were analyzed. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively correlated (p less than 0.01) with urine sodium, creatine, taurine, histidine, and...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:We investigated the endothelin (ET) receptors involved in the vasoconstrictor responses to ET-1 in rat pulmonary arteries and arterioles and the effect of endothelium removal, nitric oxide (NO) synthase inhibition, and hypoxia on ET-1-induced responses in the arteries. In isolated rat pulmonary artery rings (2-3 mm ID...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199405000-00022
更新日期：1994-05-01 00:00:00
abstract：:beta-Adrenoceptor antagonists such as propranolol and atenolol ameliorate the symptoms of human hyperthyroidism. We wished to define whether the cardiac changes of hyperthyroidism are attenuated by treatment with the beta-adrenoceptor antagonist atenolol. Rats were treated with triiodothyronine (T3) [1 mg/kg/day subcu...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:The hypothesis that local release of prostanoids may contribute to the pharmacologic effect of nitroglycerin (NTG) has long been debated. Results of prostanoid blockade by indomethacin on NTG-induced effects, to date, have been inconclusive. To quantitate the effects of intravenous indomethacin on NTG-induced myocardi...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-199712000-00005
更新日期：1997-12-01 00:00:00
abstract：:Arterial vascular resistance is established by myogenic mechanisms and is modulated both by local factors such as vasodilator metabolites and by remote controls of neurogenic and hormonal origin. This paper reports on the effects of felodipine and hydralazine on the myogenic tone and the neurogenic control of the vasc...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198710001-00019
更新日期：1987-01-01 00:00:00
abstract：:The short half-life, low plasma concentrations, and extensive biotransformation of prazosin suggest that it might be subject to extensive first-pass metabolism. Bioavailability, disposition, and hepatic extraction were studied in the dog. In conscious dogs whole blood prazosin concentrations were measured after oral a...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-197911000-00005
更新日期：1979-11-01 00:00:00
abstract：:One possible mechanism that accounts for the alterations observed in varicose veins is the activation of endothelial cells by ischemia occurring in the leg veins during blood stasis and the cascade of reactions that follows. Because in vitro data suggest that endothelium alteration is a key event in the development of...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-199901000-00002
更新日期：1999-01-01 00:00:00
abstract：:Many radioligands used to study neurotransmitter receptors label multiple subtypes or multiple classes of receptors. Frequently, two subtypes or classes of receptors coexist in the same tissue and exhibit only slightly different affinities for a radioligand. A new analytical method has been developed to quantitate the...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
abstract：:In this study, we used the spontaneously beating, isolated rat right atrium as an in vitro model to study arrhythmogenic effects of electrical stimulation. A tetrapolar platinum electrode was used for stimulation and recording of atrial electrical activity at 36.5 degrees C (spontaneous rate, 4.9+/-0.3 Hz). A flutter-...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199910000-00001
更新日期：1999-10-01 00:00:00
