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 study, we evaluated changes in brain ET levels following closed head injury (CHI) and the effects of SB 234551, an endothelin-A- (ET(A)) selective antagonist, and SB 209670, a mixed endothelin-A- and -B- (ET(A)/ET(B)) antagonist, on outcome in CHI and focal stroke. Male Sabra rats were subjected to CHI (weight drop model). Male Sprague Dawley rats were subjected to focal stroke (intraluminal suture model). Motor function(s) were assessed and immunoreactive ET (irET) and the degree of cerebral edema were measured for 24 h after CHI. Brain swelling (edema), neurological deficits and forebrain infarct volumes were measured 24 h after focal stroke. Antagonists (total doses of 7.5, 15, 30 or 60 mg/kg) were administered intravenously for 6-24 h (beginning 15 min after injury). Control rats were infused with vehicle. CHI resulted in increased ET levels in the directly contused hemisphere at 12 and 24 h. In addition, SB 234551 significantly reduced neurological deficits (decreased 30%) and brain edema (decreased 40%) following CHI (p < 0.05 at 60 mg/kg dose). SB 209670 had no effects on CHI outcome. Focal stroke studies yielded similar results. SB 234551 reduced focal stroke-induced neurological deficits by 50%, brain swelling by 54% and the degree of infarction by 36% (p < 0.05 at 30 mg/kg). SB 209670 did not provide any neuroprotection in focal stroke. These data indicate that ET plays a significant role in the pathophysiology of CHI, and that selectively targeting ET(A)-receptors similarly in both CHI and stroke might be a therapeutic opportunity.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Barone FC,Ohlstein EH,Hunter AJ,Campbell CA,Hadingham SH,Parsons AA,Yang Y,Shohami Edoi
10.1097/00005344-200036051-00104subject
Has Abstractpub_date
2000-11-01 00:00:00pages
S357-61issue
5 Suppl 1eissn
0160-2446issn
1533-4023journal_volume
36pub_type
杂志文章abstract::Bromocriptine, a dopamine (DA) receptor agonist, has been reported to have hypotensive effects in anesthetized and conscious normotensive rats but its mechanism of action is still not fully understood. Therefore, we studied the changes in mean arterial blood pressure (MAP) and heart rate (HR) elicited by an intravenou...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199109000-00003
更新日期:1991-09-01 00:00:00
abstract::To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment, 66 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than 100 and less than 115 mm Hg at the end of a 1-month washout placebo period, ...
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:10.1097/00005344-199102000-00021
更新日期:1991-02-01 00:00:00
abstract::Felodipine was compared with prazosin in patients with essential hypertension whose blood pressure was not controlled by a beta-blocking drug. One hundred patients with a supine diastolic blood pressure greater than or equal to mm Hg after 4 weeks or more on a beta-blocking drug and placebo were randomly assigned to f...
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::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
abstract::Since beta-adrenoceptor blocking drugs were originally discovered and shown to be important therapeutic agents in the management of both angina pectoris and hypertension, many other similar drugs have become available. These share the common property of beta-adrenoceptor antagonism, though they may vary in terms of po...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-198608006-00002
更新日期:1986-01-01 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::This study evaluated the 24-h antihypertensive effect of single daily doses of celiprolol, a beta-1 adrenoceptor antagonist. Patients with supine diastolic BP between 95 and 114 mm Hg started on placebo or celiprolol 200 mg daily for 2 weeks; non-responders received 400 mg daily for 2 weeks and then 600 mg daily for a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-198608004-00027
更新日期:1986-01-01 00:00:00
abstract::Coronary heart disease secondary to atherosclerosis is the leading cause of death for men in the United States. Using a new, nontransgenic, non-fat-fed mouse model of hyperlipidemia and atherosclerosis developed in our laboratory, we investigated the effect of sex on lipid profiles and subsequent aortic atheroscleroti...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200203000-00012
更新日期:2002-03-01 00:00:00
abstract::We have developed three radioimmunoassays (RIAs) of varying specificities toward the endothelin (ET) isoforms. The assays are called the endothelin-1,2[125I] assay system (RPA535), the endothelin 1-21 Specific [125I] assay system (RPA555), and the endothelin-1,2 high-sensitivity [125I] assay system (RPA545). We have f...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00121
更新日期:1991-01-01 00:00:00
abstract::We examined four commercially available human cell lines for endothelin-converting-enzyme-(ECE) like activity and compared the results with primary porcine aortic endothelial cell enzymes. The cells that were investigated were 293 (transformed primary human embryonal kidney), Hep G2 (human hepatocellular carcinoma), H...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00025
更新日期:1993-01-01 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::The human cutaneous microcirculation has so far been studied by rather crude methods, such as plethysmography and 133Xn clearance. New sophisticated and noninvasive techniques are now available, with which the microcirculation of the skin can be continuously studied and measured for hours. With two such methods, i.e.,...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198500073-00007
更新日期:1985-01-01 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::We have investigated the effects of OPC-8212, a new positive inotropic agent, and dobutamine, a known cardioselective inotropic agent, on global left ventricular (LV) and ischemic regional functions in 14 excised canine hearts with a flow-limiting stenosis of the left circumflex coronary artery (LCX) (i.e., 20-25% of ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198601000-00024
更新日期:1986-01-01 00:00:00
abstract::Epoxyeicosatrienoic acids, substrates for soluble epoxide hydrolase (sEH), exhibit vasodilatory and antihypertrophic activities. Inhibitors of sEH might therefore hold promise as heart failure therapeutics. We examined the ability of sEH inhibitors GSK2188931 and GSK2256294 to modulate cardiac hypertrophy, fibrosis, a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31827fe59c
更新日期:2013-04-01 00:00:00
abstract::Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although diff...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000092
更新日期:2014-07-01 00:00:00
abstract::Angiotensin-converting enzyme (ACE) inhibitors are widely used for treatment of heart failure after myocardial infarction (MI). The beneficial effects consist of a combination of hemodynamic effects and interference with cardiac structural alterations. These effects are believed to depend on inhibition of angiotensin ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Some calcium antagonists, including nitrendipine, were noted to cause a dose-dependent and reversible inhibition of insulin release in certain animal models. Therefore, it is important to know the effects of clinical treatment with calcium antagonists in nondiabetic or diabetic man. A review of the literature allows t...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract::Bethanidine sulfate is a congener of bretylium tosylate, which has been reported to have antiarrhythmic and antifibrillatory effects. We studied the effects of bethanidine on transmembrane potentials recorded from canine Purkinje fibers and ventricular muscle cells, using standard microelectrode techniques. Normal Pur...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198501000-00009
更新日期:1985-01-01 00:00:00
abstract::Interest in the cardiovascular protective effects of calcium channel antagonists has increased in the past decade. We investigated prevention of vascular wall remodeling by the long-acting calcium channel antagonist pranidipine in 12-week-old Dahl salt-sensitive (SS) rats with high-salt-induced (4% NaCl) hypertension....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199406000-00016
更新日期:1994-06-01 00:00:00
abstract::Vasopeptidase inhibitors are single molecules that inhibit neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) simultaneously. Omapatrilat, the first in this new class of cardiovascular agents, potentiates vasodilatory and cardioprotective peptides and represses angiotensin II. This study compared the ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199912000-00003
更新日期:1999-12-01 00:00:00
abstract::Structurally and pharmacologically diverse vasodilators are known to lower blood pressure, increase heart rate, and produce acute injury to right coronary arteries in the dog. Administration of low concentrations of endothelin-1 (ET-1) to anesthetized dogs causes coronary vasoconstriction and reductions in coronary bl...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00109
更新日期:1998-01-01 00:00:00
abstract:ABSTRACT:Establishing efficient perfusion into the myocardium is the main purpose in patients with acute coronary syndrome, but the process of reperfusion is not without risk and can damage the myocardium paradoxically. Unfortunately, there is no effective treatment for reperfusion injury, and efforts to find an effici...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000980
更新日期:2021-01-04 00:00:00
abstract::Reviewed herein are data supporting the hypothesis that insulin and the sympathoadrenal system are involved in the pathogenesis of hypertension in the obese. Data from the Normative Aging Study, a population-based cohort followed in Boston, confirm other epidemiologic reports of a direct relationship between upper-bod...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1994-01-01 00:00:00
abstract::The target proteins for calcium, when it acts as a second messenger, are a group of intracellular, specific calcium-binding proteins that contain EF-hand structures. Calmodulin regulates a number of Ca2+-dependent processes and is present in all eukaryotic cells. Parvalbumin, the S-100 proteins, two vitamin D-dependen...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1986-01-01 00:00:00
abstract::Hemodynamic responses to intravenous (i.v.) injection of DPMA [N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl] adenosine); PD 125,944], a potent adenosine agonist with a 32-fold selectivity for the adenosine-2 (A2) receptor subtype, were characterized in conscious and anesthetized rats. In conscious rats instrume...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199203000-00025
更新日期:1992-03-01 00:00:00
abstract::Twenty-four-hour urinary sodium excretion and plasma renin activity were monitored in 36 patients receiving bendrofluazide as sole antihypertensive therapy. There was no increase in urinary sodium output compared with pretreatment values during a 2-year period, and there is therefore no evidence that an increase in sa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198400061-00039
更新日期:1984-01-01 00:00:00
abstract::Nitric oxide (NO) plays a protective role in myocardial ischemia-reperfusion (I/R) injury. However, the concomitant production of superoxide and other reactive oxygen species (ROS) during I/R may diminish the bioavailability of NO and hence compromise the beneficial effects. The objective of this study was to investig...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000242050.16790.65
更新日期:2006-09-01 00:00:00
abstract::The pharmacologic profile of SK-1080, a nonpeptide AT1-selective angiotensin-receptor antagonist, was investigated by receptor-binding studies, functional in vitro assays with rabbit and rat aorta, and in vivo experiments in pithed rats. SK-1080 inhibited the specific binding of [125I]-[Sar1, Ile8]-angiotensin II to h...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199903000-00004
更新日期:1999-03-01 00:00:00
abstract::Coronary artery disease (CAD) is the major cause of death in hypertensive patients in Western populations and further efforts are required to determine how best to reduce its incidence. Large-scale placebo-controlled trials of blood pressure reduction could resolve the uncertainty about the effects of antihypertensive...
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