Abstract:
:Our recent studies have shown that the nonpeptide angiotensin II (Ang II) antagonist losartan interacts with thromboxane A2/prostaglandin H2 receptors and inhibits the thromboxane A2 (TxA2) analog U46619-induced vasoconstriction in canine coronary arteries. In this study, we further investigated whether losartan prevents TxA2-induced platelet aggregation and vasoconstriction in spontaneously hypertensive rats (SHRs). Pretreatment with losartan (10 microM) significantly reduced U46619-induced, concentration-dependent washed platelet aggregation. The inhibition is specific for losartan, because another Ang II AT1-receptor antagonist, CV11974 (10 microM), an active metabolite of TCV116, did not block the platelet aggregation caused by U46619. In addition, losartan (10 microM) augmented acetylcholine (ACH)-induced nitric oxide (NO)-dependent vasodilation and abolished the ACH-induced endothelium-derived contracting factor (EDCF)-mediated vasoconstriction in the aortic rings from adult SHRs. U46619 produced dose-dependent vasoconstriction in aortic vessels of SHRs, which was demonstrated to be blocked by the potent, selective TxA2/PGH2 receptor antagonist SQ29,548. Pretreatment with losartan (10(-6)-10(-5) M) inhibited the contractile response of U46619 and shifted the concentration-response curve to the right in a dose-dependent manner. The effective concentration at half maximal contraction (EC50) of U46619 was increased 2.5- and 7.6-fold in the presence of 1 and 10 microM losartan, respectively, without changes in maximal contraction. The active metabolite of losartan, EXP3174, at 1 microM also competitively inhibited U46619-induced contractions in aortic rings of SHRs. In contrast, neither the AT1-receptor antagonist CV11974, the AT2 antagonist PD123319, nor the angiotensin-converting enzyme inhibitor lisinopril, each at concentrations of 1 microM, had any effect on the U46619-induced constriction in aortic rings. In conclusion, losartan, acting as both AT1- and TxA2/PGH2-receptor antagonists, may enhance its therapeutic profile in the treatment of hypertension and cardiovascular disease.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Li P,Ferrario CM,Brosnihan KBdoi
10.1097/00005344-199808000-00005subject
Has Abstractpub_date
1998-08-01 00:00:00pages
198-205issue
2eissn
0160-2446issn
1533-4023journal_volume
32pub_type
杂志文章abstract::In 22 patients with stable myocardial ischemia, we prospectively studied the short- and long-term effects of isosorbide-5-mononitrate (5-ISMN) on dipyridamole-induced myocardial ischemia, the ability of dipyridamole-stress echocardiography to evaluate nitrate tolerance, and the role of activation of the neurohumoral s...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-200007000-00007
更新日期:2000-07-01 00:00:00
abstract::Spirapril (SCH 33844; 7-N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl-1,4-dithia- 7-azaspiro[4,4]-nonane-8(S)-carboxylic acid) is a new angiotensin-converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of hip-his-leu by rabbit lung ACE in a potent (Ki = 0.74 nM), selective, and noncompetitive fa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198706107-00020
更新日期:1987-01-01 00:00:00
abstract::The depressor and renal responses to the neutral endopeptidase (NEP) inhibitor, SQ 29,072, were characterized in both the conscious spontaneously hypertensive rat (SHR) and the conscious deoxycorticosterone acetate (DOCA)/salt hypertensive rat. Inhibition of tissue NEP activity by pharmacologically active doses was al...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199007000-00022
更新日期:1990-07-01 00:00:00
abstract::The "Oxford" system for continuous monitoring of the ambulatory blood pressure was used to assess the changes in blood pressure following therapy with the calcium ion antagonists verapamil and nifedipine in two separate groups of patients. In the first group 16 patients were studied on both no therapy and following a ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature characterized by elevated pulmonary artery pressure. Currently, there is no cure for this disease, and treatment is palliative. PAH therapies target 3 main pathways: prostacyclin, endothelin, and nitric oxide. The 3 distinct th...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181f89bdb
更新日期:2010-12-01 00:00:00
abstract::The acute phase of myocardial infarction promotes an inflammatory response that stimulates inducible nitric oxide synthase (iNOS). We investigated the iNOS role on the rat tail vascular bed reactivity 3 days after myocardial infarction. Vasodilator and vasoconstrictor responses were determined in isolated caudal vascu...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000156822.58081.be
更新日期:2005-04-01 00:00:00
abstract::Gangliosides, sialic acid-containing glycosphigolipids, are localized mostly to the outer leaflet of the lipid bilayer in the plasma membrane, particularly in brain. Gangliosides reduce edema formation, restore glucose metabolism, and increase cerebral blood flow after focal ischemia in the rat brain. We wished to det...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199307000-00013
更新日期:1993-07-01 00:00:00
abstract::Forty patients (aged 28-66 years) with essential hypertension were randomized to 14 weeks of treatment with diltiazem or hydrochlorothiazide (HCTZ) in a double-blind, parallel study design. A significant reduction in supine body weight (-6.0 +/- 1.5 lb; p less than 0.001) and increase in pulse (+6 +/- 2 beats/min; p l...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198704000-00002
更新日期:1987-04-01 00:00:00
abstract::The role of endothelin-B (ETB) receptor in partial ablation-induced chronic renal failure was evaluated using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the ETB receptor gene. After 5/6 nephrectomy in ETB-deficient homozygous and wild-type (+/+) rats, we measured the systolic blood p...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166316.45882.94
更新日期:2004-11-01 00:00:00
abstract::Pro-arrhythmia by noncardiac drugs has become an important safety concern in the pharmaceutical industry. The most common underlying mechanism for induction of arrhythmias by noncardiac drugs is off-target block of the native cardiac repolarizing current, I Kr. The pore-forming subunit of I Kr is encoded by the human ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31817532ee
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND:A diet rich in saturated fat and sugars (Western diet, WD) induces myocardial expression of the NLRP3 inflammasome and dysfunction in mice. We therefore hypothesized that a diet enriched with an orally available NLRP3 inflammasome inhibitor could prevent WD-induced cardiac dysfunction in mice. METHODS:Ten-w...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000628
更新日期:2018-12-01 00:00:00
abstract::In 80 patients with moderate hypertension the effects of nisoldipine 10 mg b.i.d., nifedipine 10 mg and 20 mg t.i.d., diltiazem 60 mg and 120 mg t.i.d., and verapamil 40 mg q.i.d. (all after single dose and 14 days' treatment) on blood pressure; hemodynamic parameters (cardiac output, stroke volume, left ventricular e...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::Vascular smooth muscle cell (VSMC) proliferation is pivotal in the progression of hypertension, atherosclerosis, and restenosis. Resveratrol is a grape polyphenol that is implicated as an important contributor to red wine's vascular protective effects. Its antimitogenic action on VSMC is attributed to an array of plei...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318059ae80
更新日期:2007-07-01 00:00:00
abstract::This article presents selected aspects of the presynaptic modulation of noradrenaline release from the heart. Several presynaptic effector systems that mediate either inhibition or facilitation of noradrenaline release are discussed. In particular, the potencies of muscarinic agonists and antimuscarinic drugs in musca...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198500075-00002
更新日期:1985-01-01 00:00:00
abstract::The formation of bone occurs via a series of events that are regulated by various hormones and cytokines. We previously reported that endothelin (ET) inhibits the mineralization by osteoblastic cells and natriuretic peptide (NP) promotes osteoblastic differentiation. Therefore, we attempted to identify the genes induc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00084
更新日期:2000-11-01 00:00:00
abstract::In urban Australia, the risk of retiring with hypertension is greater than 40%, and the basic abnormality--a rise in blood pressure (BP) with age--is almost universal. A hypothesis linking this with salt, therefore, concerns everyone. The diet of early humans was unsalted, and the Na content of breast milk (6 mmol/kg)...
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::We studied the short-term effects of oral administration of nisoldipine (10 mg) and propranolol (80 mg) alone and in combination in 14 patients with chronic exertional angina pectoris in a double-blind, randomized, cross-over study. The 14 patients (13 men and 1 woman, mean age 56 +/- 7 years) performed symptoms-limit...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199008000-00020
更新日期:1990-08-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) play key physiological roles and represent a significant target for drug development. However, historically, drugs were developed with the understanding that GPCRs as a therapeutic target exist solely on cell surface membranes. More recently, GPCRs have been detected on intracellula...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000196
更新日期:2015-02-01 00:00:00
abstract::The aim of this study was to examine the electrophysiological effects of isoprenaline, phenylephrine, and noradrenaline on sheep Purkinje fibers in vitro, superfused either with a normal or with a modified physiological salt solution (PSS) designed to mimic some of the conditions occurring during mild myocardial ische...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198902000-00018
更新日期:1989-02-01 00:00:00
abstract::In this study we compared the antithrombotic and anticoagulant properties of sodium and calcium derivatives of pentosan polysulfate (Na-PPS, Ca-PPS), unfractionated heparin (UFH), and low-molecular-weight heparin (Fraxiparin). The antithrombotic effects of these agents have been investigated in an experimental thrombo...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199909000-00004
更新日期:1999-09-01 00:00:00
abstract::The usual drugs for migraine attacks carry risks of increased frequency, resistance to other treatment, drug dependency, and abuse. Ergotamines may also be vascular risk factors. Alternative drugs without these risks would be useful. Flunarizine could be an alternative. Migraine cannot be reduced to molecular pathophy...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1991-01-01 00:00:00
abstract::Platelet-derived growth factor (PDGF) is a potent stimulator of growth of vascular smooth muscle cells (VSMCs). VSMCs from spontaneously hypertensive rats (SHRs) show exaggerated growth and increasingly express PDGF A-chain messenger RNA (mRNA). To examine adenovirus-mediated transfer of a ribozyme targeting the PDGF ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200206000-00011
更新日期:2002-06-01 00:00:00
abstract::Glycogen synthase kinase (GSK)-3beta inhibitors play an anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that GSK-3beta inhibitors protect against myocardial ischemia-reperfusion injury. However, the precise mechanisms remain unclear. We aimed to investigate the roles of inflam...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318186a84d
更新日期:2008-09-01 00:00:00
abstract::Nitrendipine, a calcium entry blocker, was administered by gavage (3 mg/100 g body weight/day) to rats with prolonged angiotensin-II-(AII) induced hypertension. AII was infused by osmotic minipump implanted subcutaneously. Persistent hypertension was established after 5 days. Normotensive control rats had empty sham p...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::The effects of captopril on systolic function and diastolic myocardial expansion were assessed in an open-chest multiple occlusion model of myocardial stunning. Captopril was given as a 0.25 mg/kg bolus followed by a continuous infusion at 0.25 mg/kg/h for the duration of the stunning protocol, which was initiated 30 ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199304000-00008
更新日期:1993-04-01 00:00:00
abstract::The interaction of angiotensin converting enzyme (ACE) with ramiprilat was studied at pH 7.5 in the presence of 300 mmol/l sodium chloride with furanacryloyl-Phe-Gly-Gly as substrate. Ramiprilat inhibits ACE with a Ki value of 7 pmol/l. It is both a slow- and tight-binding inhibitor; the mode of inhibition is fully co...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198706107-00005
更新日期:1987-01-01 00:00:00
abstract::The development of tolerance to the antihypertensive effect of clonidine and related imidazolines is clinically recognized. Here, we employed a restricted daytime (8:30 AM until 4:30 PM) clonidine regimen to establish a model of sustained hypotension in spontaneously hypertensive rats (SHRs). Blood pressure (BP), hear...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3180318afb
更新日期:2007-03-01 00:00:00
abstract::: Interstitial fibrosis is a common pathological change in various heart diseases, especially cardiac hypertrophy. Arginine vasopressin (AVP), one of the hallmarks of heart failure, exhibits a profibrotic effect by promoting the proliferation and differentiation of cardiac fibroblasts (CFs). In contrast, angiotensin-(...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000151
更新日期:2014-12-01 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::The vascular endothelium has a number of functions that may mediate many of the ischemia-reperfusion (IR) phenomena. The gatekeeper function is disturbed and increased capillary permeability results in edema and organ dysfunction. Vasomotor function is altered, with impairment of relaxation and augmentation of constri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199600001-00007
更新日期:1996-01-01 00:00:00