Abstract:
BACKGROUND:A substantial proportion of patients with heart failure have a normal ejection fraction and diastolic dysfunction. However, there are few data available to guide the therapy of these patients. The effects of statins on cardiac remodeling are well documented in animal models and it is reported that statin therapy revealed a survival benefit in patients with diastolic heart failure (DHF). However, the exact mechanisms of statins possibly explaining the decreased cardiovascular morbidity and mortality in patients with DHF have not been elucidated. METHODS:We used 8-week-old male C57BL/6J mice, in which angiotensin II was subcutaneously infused for 4 weeks to mimic cardiac remodeling and fibrosis. They were treated with either normal saline or pravastatin in daily doses, which did not lower the serum cholesterol levels and blood pressure. RESULTS:Pravastatin improved diastolic dysfunction in angiotensin II-induced hypertensive mice, which was associated with the amelioration of left ventricular hypertrophy and remodeling. However, statin treatment showed no effect on the increased systolic blood pressure or cholesterol levels by angiotensin II infusion. The cardioprotective effects of pravastatin were closely associated with the downregulation of collagen I, transforming growth factor-beta, matrix metalloproteinases-2 and -3, atrial natriuretic factor, interleukin-6, tumor necrosis factor-alpha, ROCK1 gene expression, and the upregulation of endothelial nitric oxide synthase gene expression. CONCLUSIONS:The beneficial effects of pravastatin on DHF and structural remodeling are through cholesterol- independent mechanism of statins or "pleiotropic" effects of statins involving improving or restoring endothelial function and decreasing vascular inflammation. These findings suggest the potential involvement of ROCK1. Thus, treatment with pravastatin might be beneficial in patients with DHF.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Xu Z,Okamoto H,Akino M,Onozuka H,Matsui Y,Tsutsui Hdoi
10.1097/FJC.0b013e31815bb629subject
Has Abstractpub_date
2008-01-01 00:00:00pages
62-70issue
1eissn
0160-2446issn
1533-4023pii
00005344-200801000-00010journal_volume
51pub_type
杂志文章abstract::In this study, we examined glyceryl trinitrate (GTN) biotransformation and cyclic GMP elevation in vascular smooth muscle before onset of GTN-induced relaxation. Isolated rabbit aortic strips (RAS) and strips of bovine pulmonary artery (BPA) and bovine pulmonary vein (BPV) were contracted submaximally and incubated wi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199005000-00005
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abstract::To evaluate the interaction between renal nerves, the atrial natriuretic peptide (ANP), and the renin-angiotensin system (RAS), electrical stimulation of renal nerves was performed in spontaneously hypertensive rats (SHR) and in their normotensive controls, Wistar Kyoto rats (WKY), before and after pharmacologic treat...
journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/00005344-199611000-00009
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abstract::From the membrane fraction of cultured human renal adenocarcinoma (ACHN) cells, two endothelin-2-converting enzymes (ECE-2A and ECE-2B) were solubilized with detergent Lubrol PX and separated by hydrophobic butyl fast-performance liquid chromatography. The pH range of the converting activity of ECE-2B for big endothel...
journal_title:Journal of cardiovascular pharmacology
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doi:10.1097/00005344-199322008-00018
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abstract::The effects of a new nitrate ester derivative, ITF 296, on large conductance and small resistance coronary arteries were investigated and compared with those of nitroglycerin and isosorbide dinitrate in chronically instrumented conscious dogs with an intact or with a deendothelialized large coronary artery. In a wide ...
journal_title:Journal of cardiovascular pharmacology
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abstract::Salusin-alpha and salusin-beta are newly identified bioactive peptides with hemodynamic and mitogenic activities. Recent studies have shown that salusins improve calcium uptake and protein synthesis in neonatal rat cardiomyocytes, suggesting that salusins may be regulatory factors for myocardial growth and hypertrophy...
journal_title:Journal of cardiovascular pharmacology
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abstract::Levosimendan is a calcium sensitizer that promotes myocyte contractility through its calcium-dependent interaction with cardiac troponin C. Administered intravenously, it has been used for nearly 2 decades to treat acute and advanced heart failure and to support the heart function in various therapy settings character...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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doi:
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abstract::BMY 20064 is a dihydropyridine Ca2+ entry blocker with potent and selective alpha 1-adrenoceptor antagonist properties. The drug was equal in potency to nifedipine as a Ca2+ entry blocker in depolarized smooth muscle preparations. It was less active than nifedipine in antagonizing Ca2+-induced contractions of isolated...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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abstract::Myocardial alpha 1-adrenoceptor number has been reported to increase during ischaemia in myocytes consequent to an increase in acyl carnitine levels. We investigated whether this phenomenon occurs in vivo and whether the novel antiischaemic agent ranolazine will protect against it. Thirty-minute occlusion of the left ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199306000-00004
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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
doi:10.1097/00005344-199302000-00001
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journal_title:Journal of cardiovascular pharmacology
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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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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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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
doi:10.1097/00005344-198906000-00008
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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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更新日期:1995-01-01 00:00:00
abstract::Chronic diabetes mellitus finally leads to serious vascular dysfunction. Diosgenin is a natural steroidal saponin with potential cardiovascular protective effect. In this study, the protective effect of diosgenin was checked on the aorta from streptozotocin-induced diabetic rats. Diabetic rats received diosgenin (40 m...
journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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