Abstract：
:The serotonin (5-HT2A) antagonistic activities and the protective effect on laurate-induced peripheral vascular lesions of AT-1015, a novel 5-HT2 receptor antagonist, were investigated. In platelet aggregation, AT-1015 selectively inhibited in vitro 5-HT2A receptor-mediated aggregation, and the activity was almost equivalent to that of ketanserin (5-HT2A/2C receptor antagonist) and 100 times more potent than sarpogrelate (5-HT2A receptor antagonist). AT-1015 also inhibited 5-HT2A receptor-mediated aggregation by oral administration in rat, and the dose required for inhibition was equivalent to ketanserin. In a 5-HT-induced vasoconstriction study in rat, AT-1015 slightly reduced maximal contraction and caused a rightward shift of the concentration-response curve (pKB value, 9.5), which was unlike competitive inhibitors such as ketanserin and sarpogrelate (pA2 value, 9.3 and 8.7, respectively). Moreover, the ex vivo inhibitory activity significantly remained after oral administration (1 mg/kg). In the rat peripheral vascular lesion model, AT-1015 (1 mg/kg, p.o.) effectively prevented progression of peripheral lesions, and it was more potent compared with ketanserin, sarpogrelate, and cilostazol. These results suggest that AT-1015 is a potent 5-HT2A receptor antagonist, and its insurmountable antagonism may be relevant to its therapeutic potential in peripheral vascular disease.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Kihara H,Hirose K,Koganei H,Sasaki N,Yamamoto H,Kimura A,Nishimori T,Shoji M,Yoshimoto Rdoi
10.1097/00005344-200004000-00002subject
Has Abstractpub_date
2000-04-01 00:00:00pages
523-30issue
4eissn
0160-2446issn
1533-4023journal_volume
35pub_type
杂志文章abstract：:The elimination of an acute oral saline load is markedly blunted in adult Sabra hypertension-prone (SBH) rats compared with hypertension-resistant Sabra normotensive (SBN) rats. Within 2 h, urinary output and the excretion of sodium and potassium are significantly reduced, while urine osmolality is markedly elevated i...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:In rats with deoxycorticosterone acetate (DOCA) salt hypertension, induction of diabetes with streptozotocin did not aggravate the elevation in blood pressure, but pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were enhanced. Along with glycosuria and hyperglycemia, ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198211000-00026
更新日期：1982-11-01 00:00:00
abstract：:Nebivolol, a chemically novel beta 1-adrenoceptor antagonist, acutely lowers blood pressure in spontaneously hypertensive rats, anaesthetised normotensive dogs, and hypertensive patients. We have investigated the actions of dl-nebivolol in five conscious normotensive rabbits (sham, mean blood pressure (BP) of 82.2 +/-...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:Left ventricular dysfunction in systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance in coronary microcirculation. We evaluated the pharmacodynamic effect of the calcium channel blocker nicardipine on left ventricular function assessed by radionuclide ventriculography in 20 patients wit...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199002000-00011
更新日期：1990-02-01 00:00:00
abstract：:Inflammation induces cardiac fibrosis and hypertrophy in multiple cardiovascular diseases, contributing to cardiac dysfunction. We tested the hypothesis that pentoxifylline (PTX), a phosphodiesterase inhibitor with anti-inflammatory property, would attenuate cardiac fibrosis and hypertrophy, and prevent cardiac dysfun...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0000000000000316
更新日期：2016-01-01 00:00:00
abstract：:alpha-Adrenoceptor agonists and antagonists are widely used perioperatively for internal mammary artery (IMA)-coronary artery bypass operations. To determine subtypes of alpha-adrenoceptors in the human IMA, we studied responses of isolated human IMA segments to alpha-adrenoceptor agonists, antagonists, and electrical...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:Hypertension is a well-known risk factor that predisposes to the development of left ventricular hypertrophy, coronary flow abnormalities, and systolic and diastolic dysfunction. This complex of abnormalities is known as hypertensive heart disease and eventually leads to heart failure. Structural lesions underlying th...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-199800003-00003
更新日期：1998-01-01 00:00:00
abstract：:Cardiac remodeling is regulated by an extensive intracellular signal transduction network. Each of the many signaling pathways in this network contributes uniquely to the control of cellular adaptation. In the last few years, it has become apparent that multimolecular signaling complexes or "signalosomes" are importan...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/FJC.0000000000000206
更新日期：2015-03-01 00:00:00
abstract：:We have recently shown that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1-H-imidazoe l h...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200036051-00034
更新日期：2000-11-01 00:00:00
abstract：:Serotonin, applied to helical strips of larger vessels such as coronary arteries, acts as a potent vasoconstrictor in vitro. In contrast, in vivo serotonin causes a remarkable decrease in total peripheral resistance. To differentiate the influence of serotonin on resistances of large and small vessels, experiments wer...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198500077-00017
更新日期：1985-01-01 00:00:00
abstract：:A single dose of doxazosin, a long-acting postsynaptic alpha 1-adrenoceptor antagonist, was administered to seven patients with essential hypertension. Following administration of a single dose, all the patients except one who was forced to be discharged from the hospital for work, continuously received doxazosin once...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198707000-00013
更新日期：1987-07-01 00:00:00
abstract：:Coronary arteries from animals on normal diets (ND) exhibit well-maintained responses to dilators under ischemic conditions. The reported altered metabolic requirements and K+-currents in blood vessels from hypercholesterolemic animals fed high-fat diets (HF) led us to hypothesize that under metabolically depressed co...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200404000-00004
更新日期：2004-04-01 00:00:00
abstract：:Dilevalol, the stereoisomer of labetalol, was given in repeated incremental intravenous bolus injections to 10 patients with severe hypertension requiring urgent blood pressure lowering. The mean cumulative dose of dilevalol was 445 +/- 165 mg. Blood pressure was reduced from 201 +/- 33/131 +/- 13 to 150 +/- 12/109 +/...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:21-Aminosteroids are a group of new synthetic compounds developed as antiperoxidants. Although several studies have demonstrated their cardioprotective properties in acute ischemic models, none has assessed their long-term benefits after chronic myocardial infarction. In this investigation, we examined the cardioprote...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199912000-00013
更新日期：1999-12-01 00:00:00
abstract：:The similarity between the metabolic pathways of serotonin in platelets and serotoninergic nerve endings has often been emphasized. The turnover of serotonin was therefore investigated in two diseases: hypertension (as central serotoninergic neurones appear to modulate central sympathetic nervous activity) and depress...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198500077-00003
更新日期：1985-01-01 00:00:00
abstract：:Nineteen hypertensive patients were treated with increasing doses of the new angiotensin-converting enzyme inhibitor MK 421. Twenty milligrams orally reduced blood pressure from 180/112 +/- 6.8/3.6 (mean +/- SEM) to 160/100 +/- 6.5/3.3 mm Hg (p less than 0.005) while heart rate increased from 75 +/- 2 to 87 +/- 3 beat...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:Currently, the effects of the thrombolytic drugs are tested in vivo in dog or rabbit models that require a relatively large amount of the drug. The goal of the present study was to describe a new model that would allow one to test the in vivo thrombolytic effect of drugs with a limited amount of compound. For this pur...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198811000-00004
更新日期：1988-01-01 00:00:00
abstract：:Clinical trials in patients with congestive heart failure have shown a wide disparity in the hemodynamic responses to chronic therapy with newer positive inotropic drugs. Therefore, the long-term efficacy of enoximone was studied in 10 patients with severe congestive heart failure. Patients were evaluated clinically, ...
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 objective of this study was to investigate the cardioactive properties of oxybutynin, a drug that is widely prescribed for management of voiding dysfunction. Membrane currents were recorded from whole-cell-configured guinea pig ventricular myocytes, and action potentials were recorded from guinea pig and rabbit pa...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200002000-00024
更新日期：2000-02-01 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：:Relative DA1-dopamine-receptor agonist and alpha-adrenoceptor antagonist activities of fenoldopam were determined in pentobarbital anesthetized dogs. The renal vasodilating effect of intravenous infusions of fenoldopam was used as an index of its DA1-agonist activity. Inhibition by fenoldopam of femoral vasoconstricti...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198801000-00018
更新日期：1988-01-01 00:00:00
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journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities;...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181fd341c
更新日期：2011-01-01 00:00:00
abstract：:The actions of SK&F 94120, a selective phosphodiesterase (PDE III) inhibitor, have been characterised on human ventricular myocardium obtained from heart failure patients. Some actions have been compared directly with those of the drug on guinea pig and cat ventricular myocardium. SK&F 94120 caused positive inotropic ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198706000-00013
更新日期：1987-06-01 00:00:00
abstract：:Epidemiologic studies of recent years have demonstrated an association between low plasma high-density lipoprotein (HDL) cholesterol levels and the development of atherosclerosis. The PROCAM (Prospective Cardiovascular Münster) study has identified HDL cholesterol as the single parameter predictor with the highest pot...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1990-01-01 00:00:00
abstract：:The effects of acetaldehyde (ACA) were examined in isolated electrically driven papillary muscle preparations from normal and streptozotocin-treated diabetic rats. Muscles from diabetic rats developed greater tension than those from normal rats. In muscles from both groups, ACA caused concentration-dependent negative ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:The prevention of coronary disease in hypertensive patients will see progress in the years to come. It is clearly too much, however, to expect this progress to come exclusively from the application of new therapies, as the incidence of coronary disease in hypertensive patients depends on several factors, which are, es...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1990-01-01 00:00:00
abstract：:Autoradiographical images of whole body sections from control mice (29 +/- 3 days old) revealed high ETA densities within the cardiovascular system, with ETB receptors predominating in the kidney. A similar distribution of ETA receptors was found in ETB-deficient mice (25 +/- 2 days old) but the density was reduced in...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/01.fjc.0000166284.08657.64
更新日期：2004-11-01 00:00:00
abstract：:In a double blind, randomized placebo-controlled crossover study we characterized how terbutaline affects the mean and short-term fluctuations of peripheral vascular resistance and arterial compliance. The study was carried out in six young and healthy male subjects in the supine and upright positions by recording con...
journal_title：Journal of cardiovascular pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1097/00005344-200407000-00010
更新日期：2004-07-01 00:00:00
abstract：:Endothelial damage triggers platelet adhesion and platelet-associated prothrombinase formation at the point of injury, resulting in the progression of thrombus formation. The present study compared the inhibitory effects of fondaparinux, an indirect factor Xa (FXa) inhibitor, and TAK-442, a direct FXa inhibitor, on pl...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e31820382a9
更新日期：2011-02-01 00:00:00
