Abstract：
:The pharmacologic profile of a novel angiotensin I (AT1) receptor antagonist 606A was studied in various in vitro and in vivo preparations. The 606A showed a high affinity at AT1 receptors [inhibition constant (Ki), 12.8 +/- 0.4 nM] in rabbit adrenal cortical membrane and a low affinity to AT2 receptors (Ki, > 1 mM) in bovine cerebellar membrane, indicating potent and selective AT1 properties. In the guinea pig aorta, 606A reduced the maximal angiotensin II-induced contraction (pD'2, 9.06 +/- 0.04), whereas EXP3174 showed suppression of the maximum response and a shift to the right of the concentration-response curve at lower and higher concentrations, respectively (conventionally calculated pd'2, 8.61 +/- 0.23). The 606A had no effects on KC1-, norepinephrine-, serotonin-, and endothelin-1-induced contractions or any agonist activities. In anesthetized dogs, 606A inhibited the angiotensin II-induced pressor response 35 times more potently than losartan. In renal hypertensive rats and spontaneously hypertensive rats (SHRs), 606A decreased systolic blood pressure 10 and 3 times more potently than losartan, respectively, without any chronotropic effects. By repeated administration of 606A to SHRs for 2 weeks, an augmentation of the hypotensive effect was observed No rebound phenomena occurred after discontinuation. These results indicate the 606A is a potent AT1-selective insurmountable angiotensin II receptor antagonist having more potent angiotensin II receptor antagonistic and hypotensive effects than losartan in in vivo models. 606A is suggested to be a useful agent for the treatment of patients with hypertension.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Hashimoto Y,Harada Y,Narita H,Naito K,Murata Sdoi
10.1097/00005344-199702000-00019subject
Has Abstractpub_date
1997-02-01 00:00:00pages
284-90issue
2eissn
0160-2446issn
1533-4023journal_volume
29pub_type
杂志文章abstract：:Roughly 40% of all diabetics, whether insulin dependent or not, develop persistent albuminuria, a decline in their glomerular filtration rate, and elevated blood pressure, i.e., diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-199219006-00004
更新日期：1992-01-01 00:00:00
abstract：:Mikania laevigata, popularly known in Brazil as guaco, is widely used for respiratory disorders. As this plant is rich in coumarins, there is evidence of indications that it may cause bleeding and therefore should not be used concomitantly with anticoagulants. The basis of this information is very theoretical, with no...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0000000000000745
更新日期：2019-12-01 00:00:00
abstract：:The effect of two calcium antagonists on left ventricular (LV) relaxation and diastolic filling was evaluated in 16 randomized patients. Isradipine and nifedipine were administered intravenously in a maximum dose of 60 micrograms/min for isradipine and 63 micrograms/min for nifedipine. Heart rate was increased signifi...
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：1990-01-01 00:00:00
abstract：:Acetazolamide (ACTZ) vasodilating properties are used for the assessment of cerebral vasodilatory reserve not only in cerebral pathology investigation, but also in clinical pharmacology studies. However, the kinetics of these vasodilating properties are not clearly established; moreover, the cerebral selectivity of AC...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199511000-00022
更新日期：1995-11-01 00:00:00
abstract：:Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, and MBK3) were generated by somatic cell fusion, characterized by their peptide specificity, and compared with the known ligand specificity of the kinin receptor subtypes. By these criteria, the paratope of MBK3 resembled the B2 receptor binding site,...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:The vulnerable period (VP) is an interval of time during the cardiac cycle within which premature stimulation may lead to trains of responses (one: many stimulus-response coupling). Although the VP parallels the recovery of sodium channel availability, modulators of its boundaries remain unclear. Numerical studies of ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:Endothelins (ETs) are a family of peptide hormones that act on G protein-coupled ET(A) and ET(B) receptors. ETs exert inotropic and chronotropic actions in the heart. Myocardial ischemia is associated with increased plasma levels of ET and cell swelling. We examined the effect of ETs on dog atrial swelling-induced chl...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200005000-00014
更新日期：2000-05-01 00:00:00
abstract：:The development of numerous types of cardiovascular disease is associated with alteration of the vascular smooth muscle cell (SMC) phenotype. We have previously shown that abdominal aortic aneurysm progression in a mouse model of the disease is associated with reduced differentiation of SMCs within the lesion and that...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0000000000000395
更新日期：2016-08-01 00:00:00
abstract：:The present study has been designed to explore the beneficial effect of rosiglitazone, a peroxisome proliferator activated receptor-gamma agonist, in hyperhomocysteinemia-induced cardiac hypertrophy in rats. The hyperhomocysteinemia was induced in rats by feeding L-methionine (1.7 g/kg per day orally) for 8 weeks. The...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e3181de308b
更新日期：2010-07-01 00:00:00
abstract：:We designed an experimental animal study to study the effects of dopamine (DA) on diastolic function in hypothermia. DA was applied at five incremental infusion rates in 6 sheep during normothermia and moderate hypothermia (29 degrees C). Left ventricular end-diastolic pressure (LVEDP) was increased during hypothermia...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199405000-00002
更新日期：1994-05-01 00:00:00
abstract：:Analysis of the circadian distributions of silent ischemic episodes and myocardial infarction has revealed a circadian variability with peak event incidences in the morning hours after awakening. This morning peak of ischemic events is paralleled by circadian variations of blood pressure and heart rate that reflect an...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-199321002-00008
更新日期：1993-01-01 00:00:00
abstract：:Increased levels of endothelin (ET) have been demonstrated in the ischemic brain, and ET receptor antagonism has been shown to improve outcome in cerebral ischemia. However, no previous work has been carried out evaluating the role of ET and its antagonism in brain trauma as compared to experimental stroke. In this st...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200036051-00104
更新日期：2000-11-01 00:00:00
abstract：:The electrophysiologic and antiarrhythmic effects of oral and intravenous UM424 were studied in canine models of acute and chronic myocardial injury. In the first phase of this study, reentrant ventricular tachyarrhythmias and/or ventricular fibrillation were initiated by programmed electrical stimulation techniques i...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198503000-00001
更新日期：1985-03-01 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：:During myocardial ischemia, the extracellular potassium concentration increases in a triphasic pattern, an initial early increase, a constant phase, and a late increasing phase. The aim of this study was to determine whether diltiazem inhibits the late increasing phase by maintaining glycolytic adenosine triphosphate ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199710000-00004
更新日期：1997-10-01 00:00:00
abstract：:LY53857, spiperone, ketanserin, and setoperone were potent and competitive 5-HT2-receptor antagonists in the rat jugular vein with equivalent affinities at 5-HT2 receptors. In the rat jugular vein, ritanserin blocked 5-HT2-mediated contractile responses with a depression of the maximum response in concentrations great...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
abstract：:The antiarrhythmic efficacy and proarrhythmic potential of the class IC antiarrhythmic agent encainide were assessed in subacute and chronic postinfarction canine models, respectively. In conscious dogs with spontaneous premature ventricular complexes (PVCs) at 48 h after anterior myocardial infarction (MI), cumulativ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199303000-00008
更新日期：1993-03-01 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：:We recently found that TGF-beta increases ET-1 secretion in MDCK, a renal tubular cell line. The secretion of ET-1, by a confluent monolayer of MDCK cells grown on a filter, to the basolateral side of the epithelium was two times greater than that to the apical side. However, TGF-beta-increased ET-1 and big ET-1 secre...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199100177-00065
更新日期：1991-01-01 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：:Because the role of sodium channels in the initiation and maintenance of VF is not fully elucidated, we studied the significance of sodium channel activity in VF using sodium channel blockers. In nonischemic isolated feline hearts, the following electrophysiologic parameters were measured before and after application ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-200012000-00015
更新日期：2000-12-01 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
abstract：:Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199212000-00017
更新日期：1992-12-01 00:00:00
abstract：:At present, endothelin (ET) receptor classification remains controversial. We investigated the presence of atypical ETA receptors in human saphenous veins (SV). Human SV was obtained from 24 patients undergoing coronary artery bypass grafting. Vessels were set up in organ baths, stretched to a tension of 6 g, and left...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-199800001-00049
更新日期：1998-01-01 00:00:00
abstract：:It has been recently suggested that atrial natriuretic factor (ANF) might be involved in the physiological regulation of pulmonary circulation. Therefore, we investigated the pulmonary hemodynamic response to 20-min infusions of 0.05, 0.1, and 0.2 micrograms kg-1 min-1 of alpha human ANF in five dogs alternatively ven...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/00005344-198912000-00007
更新日期：1989-12-01 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：:There is increasing interest in initial therapy of hypertension with sympatholytic agents and the influence of antihypertensive therapy on cardiac and renal function. We treated 26 men with essential hypertension with either guanabenz alone (n = 14) or propranolol alone (n = 12) and assessed blood pressure and renal p...
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：1984-01-01 00:00:00
abstract：:The enantiomers of tocainide, a Class Ib antiarrhythmic agent, have recently been shown to exhibit differences in antiarrhythmic activity and pharmacokinetic characteristics. The present study examined the antiarrhythmic and electrophysiological effects of SR tocainide, S tocainide, and R tocainide on arrhythmias in a...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Insulin resistance is a frequent phenomenon and a marker of increased risk for non-insulin-dependent diabetes mellitus (NIDDM) and atherosclerosis. According to recent estimations, not only individuals with obesity, NIDDM, and impaired glucose tolerance (IGT) but also one fourth of the "healthy" glucose tolerant and t...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章,评审
doi：10.1097/00005344-199200111-00004
更新日期：1992-01-01 00:00:00
abstract：:Acute discontinuation of statins induces vascular dysfunction and increases cardiovascular events. The mechanisms underlying these events are under investigation. We showed an increase in angiotensin II (AngII) signaling after acute statin withdrawal. We investigated whether AngII-AT1-receptor expression (AT1-R mRNA) ...
journal_title：Journal of cardiovascular pharmacology
pub_type： 杂志文章
doi：10.1097/FJC.0b013e318157c0b2
更新日期：2007-12-01 00:00:00
