Abstract:
:We observed that heterozygous knockout (+/-, KO) of either endothelin-A- (ET(A)) or -B- (ET(B)) receptors significantly reduced the pressor responses to systemically administered endothelin-1 (ET-1) in ET(A) or ET(B) (+/-) KO mice when compared to wild-type (WT) mice (data not shown). Also, we observed that basal mean arterial pressure (MAP) is significantly higher in ET(B) (+/-) (92.7 +/- 1.2 mmHg) (n = 53, p < 0.05) but not ET(A) (+/-) KO mice (70.6 +/- 1.8 mmHg) (n = 23) when compared to their anaesthetized WT littermates (70.1 +/- 0.7 mmHg) (n = 118). A 90 min treatment with either BQ-123 (10 mg/kg), an ET(A)-selective antagonist, or BQ-928 (10 mg/kg), a mixed ET(A)/ET(B) antagonist, administered intraperitoneally, significantly reduced basal MAP of ET(B) (+/-) KO mice almost to the level of their WT treated counterparts (94.9 +/- 4.9 mmHg) (n = 6) vs (+ BQ-123: 59.7 +/- 0.3 mmHg, n = 8); (+ BQ-928: 72.4 +/- 2.6 mmHg, n = 5). It is worthy of note that BQ-123 significantly reduced basal MAP in WT mice but to a lesser extent than in ET(B) (+/-) KO mice (69.6 +/- 2.3 mmHg, n = 8) vs (+ BQ-123: 57.3 +/- 1.4 mmHg, n = 8). In contrast, the ET(B)-selective antagonist, BQ-788 (10 mg/kg i.p.), had no significant effect on MAP even after 90 min of treatment (ET(B) (+/-) KO: (92.3 +/- 2.3 mmHg, n = 6) vs (+ BQ-788: 89.7 +/- 3.1 mmHg, n = 6); WT: (70.5 +/- 3.7 mmHg, n = 7) vs (+ BQ-788: 71.2 +/- 2.0 mmHg, n = 6). Therefore heterozygous KO of either ET(A)- or ET(B)-receptors significantly alters the phenotypic pressor properties of ET-1. We also suggest that there is less ET clearance in ET(B) (+/-) KO mice than in WT mice, which can explain the ET(A)-dependent hypertensive state of the former strain.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Berthiaume N,Yanagisawa M,D'Orléans-Juste Psubject
Has Abstractpub_date
2000-11-01 00:00:00pages
S72-4issue
5 Suppl 1eissn
0160-2446issn
1533-4023journal_volume
36pub_type
杂志文章abstract::Diabetic nephropathy is a major cause of end-stage renal failure and the mortality rate due to this disease is continuously progressing worldwide. The multifaceted signalling mechanisms have been identified to be involved in the pathogenesis of diabetic nephropathy. Despite the modern therapies like antidiabetics, ant...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e3181ad2190
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abstract::Congestive heart failure is a leading cause of morbidity and mortality. Congestive heart failure is marked by atrial and ventricular enlargements and reduced cardiac contractility and an association with an increased incidence of atrial and ventricular arrhythmias and sudden cardiac death. Dysfunctional ion channel fu...
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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::Cardiovascular function is regulated by short-term and long-term neurohormonal and autocrine-paracrine mechanisms that act synergistically or sequentially. Structural adaptive changes that occur progressively over time also contribute to the long-term outcome. The renin-angiotensin system (RAS) can operate as both an ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1989-01-01 00:00:00
abstract::Neonatal exposure to a selective serotonin reuptake inhibitor (SSRI) leads to decreased left ventricular volumes and sympathetic activation in adult mice. We hypothesized this neonatal SSRI exposure-induced small left heart syndrome would increase post-myocardial infarction (MI) morbidity and mortality. C57BL/6 mice r...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199511000-00012
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abstract:BACKGROUND:S-equol is known as an estrogenic substance, but its ability to restore vascular endothelial function is unknown. The aim of this study was to investigate the impact of S-equol on endothelial function and intimal thickening under isoflavone- and estrogen-deficient circumstances. METHODS:Twelve-week-old fema...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000220
更新日期:2015-05-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/FJC.0000000000000944
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200202000-00001
更新日期:2002-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181b2b72b
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abstract::To evaluate a possible mechanism for the chronic regulation of MAPK/ERK kinase-1 (MEK-1) and p42 mitogen-activated protein kinase (MAPK) we studied the long-term effects of the G-protein-coupled receptor agonist endothelin-1 (ET-1) and the protein tyrosine kinase-coupled receptor agonist platelet-derived growth factor...
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 investigated the effects of a class I antiarrhythmic drug, cibenzoline, on human atrial muscle in vivo. Electrophysiologic measurements were performed in 44 patients (mean age 49 +/- 15 years), before and after an intravenous infusion of cibenzoline 1.4 mg/kg in 5 min. Extrastimuli at a basic cycle length (BCL) of ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199608000-00020
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181dd0ec2
更新日期:2010-07-01 00:00:00
abstract::Independent determinations of Ca2+ by two indicators showed that subcellular Ca2+ activity (intracellular free calcium concentration) was heterogeneous in rat myocardial cells. Arsenazo III (Az III), a membrane-impermeant absorbance indicator for Ca2+, was loaded into cardiac muscle via liposomes and calcium quantitat...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::To assess the role of angiotensin II (AII) in development of myocardial injury during ischemia and reperfusion, the effects of short-term treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril were compared with the effects of short-term treatment with L-158,338, an AII antagonist, in isolated wor...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199410000-00008
更新日期:1994-10-01 00:00:00
abstract::The aim of the present study was to investigate the putative role of endothelin (ET) in mediating ischemia/hypoxia-induced ANP release utilizing exogenous ET-1 or ET receptor antagonists (BQ-123 or Bosentan). Isolated rat hearts with non-distended atria were perfused using a Langendorff apparatus and heart rate mainta...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200402000-00010
更新日期:2004-02-01 00:00:00
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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::The present study was designed to evaluate the effects of big endothelin (ET) on renal hemodynamics and excretory functions in rats with experimental congestive heart failure (CHF) produced by aortocaval fistula. Clearance studies were performed in control and in chronic (7 day) CHF rats. Administration of bit ET (1 a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00005344-199509000-00018
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章
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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
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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